Total Synthesis of Rapamycin
|
|
|
- Daniel Copeland
- 5 years ago
- Views:
Transcription
1 . sman, CEM 20 //2007 Total ynthesis of Rapamycin Matthew L. Maddess, Miles. Tackett, idenori Watanabe, Paul E. ennan, Christopher D. pilling, James. cott, David P. sborn, and teven V. Ley* Angew. Chem. Int. Ed. 2007, 6, Presented by: ami sman Jan. nd Introduction Me (-)-rapamycin () 9 Me Me First isolated in 975 from treptomyces hygroscopicus found in Easter Island soil Recognized for its potent immunosuppressive action Blocks entry of resting immune cells into the cell cycle Blocks progression of cells in the early phase of the cell cycle, causing cell cycle arrest Mammalian target for rapamycin is serine/threonine protein kinase Involved in intracellular events such as proliferation, growth, differentiation, migration, and survival. -chreiber,. L. Cell 992, 70, chreiber,. L. et. al. Angew. Chem., In. Ed. Eng. 992, 3, -00
2 . sman, CEM 20 //2007 Previous yntheses Me (-)-rapamycin () 9 Me Me previous total syntheses First synthesis of naturally occurring enantiomer was by the icolaou group Then came the chreiber group with their synthesis, using the Evans-Tischenko reaction, and later in the synthesis the Mukaiyama macrocyclization. The Danishefsky group completed their synthesis, highlighting at the end of the synthesis the aldol reaction via Ti enolate, to the macrocycle structure. Finally the mith group came with their synthesis longest linear sequence from first point convergence of steps first synthesis of Demethoxy-rapamycin convergent approach permitted straight forward preparation of analogs. -K.C. icolaou et. al., JAC 993,, 5, 9 -. L. chreiber et. al., JAC 993, 5, J. Danishefsky et. al., JAC 993, 5, 935 -A. B. mith et. al. JAC 995, 7, 507 Retrosynthetic Analysis Me (-)-rapamycin () 9 Me Me TB PMB R 2 PMB Me C-C electrophile 5 Me TB Me 20 C-C20 lactone 3 I R C2-C stannane 2 TE C-C bromide Me 33 C33-C epoxide 6 Me 3 n 2
3 . sman, CEM 20 //2007 ynthesis of C-C bromide Me 9 Me Me 7 Tr. (CCl) 2, DM DIPEA, C 2 Cl 2 2. (C 2 ) 3, BF 3.Et 2, C 2 Cl 2, -78 o C - RT, 99% over two steps. LiBEt 3, TF, 0 o C, 99% Kinetic bromoalkene, only isomer dedected. 3.Py, DM, DIPEA, C 2 Cl 2, 0 o C 2. KMD, [8]crown-6, C 2 Me (CF 3 C 2 ) 2 P()C 2 C 2 Me, 2,TF, 96% over two steps MsCl, Et 3, DMAP, C 2 Cl 2, then Li, DMF, 70%. DIBAL-, C 2 Cl 2, -5 o C, 99% ynthesis of C-C Electrophile 5 2. Lipase P-30 (8wt%), DME/ vinyl acetate (5:), r.t., h, 75%, 96-99%ee. TBCl, Im, C 2Cl 2 2. K 2C 3, Me 3. a, PMPCl, TBAI, TF. TBAF, TF, 90% over four steps. R 3 R=Ac R=PMB. 3.Py, DM, DIPEA, C 2 Cl 2, 0 o C, 99% for both 3 &. 5 R=Ac R=PMB R. sbuli, allylmethyl ether, TF, -78 o C, then (-)-(Me)BIpc 2, then BF 3.Et 2, then 5, h, then 3 a, 30% 2 2, -78 o C - RT 2. K 2C 3, Me, r.t., 0% over two steps Me 9 Me Me PMB PMB. s, M, acetone/ water, r.t., 78% PMB PMB. a, PMBCl, TBAI, DMF, r.t,99% Me 9 Me 8 Me 7. Pb(Ac), Ph, 99% PMB PMB Me 5a own alkoxyallylation (5 to 7) selectivity was confirmed by X-ray analysis Direct ozonolysis of 8 was problematic. 3
4 . sman, CEM 20 //2007 ynthesis of C-C Electrophile 5 R Me R R. LiMD, TF, o C, then Ac, 82% for 5, 92% for Me R 2Me 5 R=Ac R=PMB Me R=Ac 23 R=PMB. PMB-TCA, TrBF (5mol%), TF, r.t., 7% Me 9 Me Me PMB Me 5b PMB. CA, Me, r.t., 80% 2. Ag 2, MeI, C 2Cl 2, 50 o C, 7% 3. LiMD, Me(Me). Cl, TF, -20 o C-- o C, 97% PMB PMB 2 Me Me econd approach for electrophile 5 using the groups recently developed butane-2,3-diacetal (BDA, 2). BDA allowed for a highly selective aldol condensation with 5 or. ynthesis of C-C Fragment TEPMB 26 Me. tbuli, TF, -96 o C, then 5a, -96 o C to -78 o C, 66% PMB. 3.Py, DM, DIPEA, C 2Cl 2, 0 o C, 99% 2. Zn(B ) 2, Et 2, -20 o C, 3days, 80% 3. TETf, 2,6-lutidine, C 2Cl 2, -78 o C, 0min, 99% + Me PMB Me PMB PMB 25a 25a/25b 3: PMB 25b Me 9 Me Me. tbuli, TF, -96 o C, then 5b, -96 o C to -78 o C, 80% Me PMB 27 PMB. Zn(B ) 2, Et 2, -20 o C, 2h, 83% 2. TECl, Im, DMF, 50 o C, 93% TEPMB Zn(B ) 2 afforded correct stereochemistry Addition of and Weinreb amide 5b offered higher yields to give 27 without any diastereomeric mixtures. Control D 2 studies indicated C-C vinyl bromide cleanly transmetalated, without abstraction of from C dithiane. Me PMB
5 . sman, CEM 20 //2007 TB Me ynthesis of C-C Fragment Me TEPMB 26 PMB TB Me. 6, tbuli, TF/MPA(5:), -78 o C to -0 o C, 77%. TF/Me/ 2 (:9:), PhI(CCF 3) 2, r.t., 8% 2. 30, DCC, DMAP, C 2Cl 2, -5 o C, 2h, 8% 3. DDQ, p 7 buffer, C 2Cl 2, r.t., 93%. (CCl) 2, DM, Et 3, C 2Cl 2, 99% Me PMB TE PMB Me 9 Me Me 3 Me C TE TB Me 6 C 2 30 TB Me ynthesis of C-C Fragment Me TEPMB PMB TB Me. 6, tbuli, TF/MPA(5:), -78 o C to -0 o C, 8%. TF/Me/ 2 (:9:), PhI(CCF 3) 2, r.t., 83% 2. 30, DCC, DMAP, C 2Cl 2, -5 o C, 2h, 99% 3. DDQ, p 7 buffer, C 2Cl 2, r.t., 90%. (CCl) 2, DM, Et 3, C 2Cl 2, 99% Me PMB TE PMB Me 9 Me Me 3 Me C TE TB Me 6 C
6 . sman, CEM 20 //2007 Final tage of ynthesis TB TB Me. CrCl 2, CI 3, TF, 0 o Me C to RT, 82% 2. [Pd(PFur 3) 2Cl 2], (Me 3n) 2, MP, dark, RT, 68% Me 3 Me C TE 2a Me Me 3n TE 9 Me Me TB Me Me Alloc Me 0 TE. LiAl(tBu) 3, TF, - o C, 8% 2. Alloc-Cl, -pyrrolidinopyridine, C 2Cl 2, 8%. [Pd(PFur 3) 2Cl 2], 3, MP, dark, RT, 69% TB Me Me Me TE o minor geometric isomer was detected of the tille coupling Possibly Z isomer of 3 equilibrated with the E, or Z isomer react slower than E isomer Me I 3 (E/Z 6:) Final tage of ynthesis 0. 0.M Li in 2,TF, 0 o C, 89% 2. TETf, 2,6-lut, C 2Cl 2, -20 o C to RT, 88% 3. C 2C 2, 2,6-lut, C 2Cl 2, -20 o C, 66% TB Me Me Alloc Me Me 2C TE 9 Me Me TB. LiMD, TF, -78 o C to -20 o C, 78% 2. [Pd(PPh 3) ], dimedone, TF, RT, 80% TB TE. catechol, DCC, DMAP, C 2Cl 2, 0 o C to RT, 88% 2. K 2C 3, DMF, RT, 8% Me Me Me TE Me 3 TE Alloc Me Me TE TE equence of events from 0 to is crucial to avoid epimerization of C Methy group. 6
7 . sman, CEM 20 //2007 Final tage of ynthesis TB Me Me TE Me. PhI(Ac) 2, C 3 C/ 2 (:), 0 o C 2. DMP, Py, C 2Cl 2, RT, 6% over two steps TE TB Me Me TE Me TE 3. F.Py, TF, 50 o C, 6% Me 9 Me Me (-)-rapamycin ummary ew and efficient convergent route to the synthesis of (-)-Rapamycin Used their recently developed butane-2,3-diacetal chemistry as protecting and stereodirecting functionality for the aldol reaction Efficient macroetherification/catechol strategy for the formation of the macrocyclic core of rapamycin. 7
Synthesis of Azadirachtin: A Long but Successful Journey
ynthesis of Azadirachtin: A Long but uccessful Journey Gemma E. Veitch, Edith Beckmann, Brenda J. Burke, Alistair Boyer, arah L. Maslen, and teven V. Ley Angew. Chem. Int. Ed. 2007, Early View And Gemma
Synthetic Developments Towards the Preparation of Erythromycin and Erythronolide Derivatives
ynthetic Developments Towards the Preparation of Erythromycin and Erythronolide Derivatives Russell C. mith Denmark Group Meeting 8-9-2005 most extensive project in organic synthesis this phenomenon is
Hennoxazole A. Philip Williams Group Meeting December 12, OMe. OMe 1 6 O H
ennoxazole A 1 6 11 17 24 Philip Williams Group eting December 12, 2007 Discovered Discovered by Paul cheuer at the University of awaii in 1991. Isolated 480mg ennoxazole A from 4.5kg from the sponge Polyfibrospongia
SECTION 12. «POT-POURRI» in Organic Synthesis (2018)
SECTIN 12 «PT-PURRI» in rganic Synthesis (2018) 1 Total Synthesis of Erythromycin A via a Spiroketal ERYTRMYCIN A DESLNGCAMPS et al. Can. J. Chem. 1985, 63, 2810-2820. 2 Tetrahydropyran Derivative as Starting
Highly Cytotoxic, Structure Similar Polyke>des CO 2 H
Current Literature Anguinomycins and Deriva2ves: Total Syntheses, Modeling, and Biological Evalua2on of the Inhibi2on of Nucleocytoplasmic Transport liv Eidam, Ulrike Kutay, Karl Gadermann, et al, JACS,
Total Synthesis of Rapamycin**
Natural Products Synthesis DOI: 10.1002/anie.200604053 Total Synthesis of Rapamycin** Matthew L. Maddess, Miles N. Tackett, Hidenori Watanabe, Paul E. Brennan, Christopher D. Spilling, James S. Scott,
James D. White. A very productive professor 64 students graduated from his lab 94 postdocs have worked in his lab. Education Experience
A very productive professor 64 students graduated from his lab 94 postdocs have worked in his lab Education Experience Fraser Fleming University of Drexel Pavel agory University of Michigan Cambridge University,
Total Synthesis of Peloruside A Through Kinetic Lactonization and Relay Ring-Closing Metathesis Cyclization Reactions
Total Synthesis of Peloruside A Through Kinetic Lactonization and Relay Ring-Closing Metathesis Cyclization Reactions Thomas R. oye, Junha Jeon, Lucas C. Kopel, Troy D. Ryba, Manomi A. Tennakoon, and Yini
Massachusetts Institute of Technology Organic Chemistry 5.512
Massachusetts Institute of Technology rganic Chemistry 5.512 Problem Set 6 Solutions Stereocontrolled Carbonyl Reduction and Aldol Reactions May 5, 2006 Lucy Kohnen ( The target compound was used as an
Total Synthesis of Oxazolomycin A
Total Synthesis of xazolomycin A Me xazolomycin A Me Eto, K.; Yoshino, M.; Takahashi K.; Ishihara, J.; atakeyama S. rg. Lett. 2011, 13, 5398 Dimas Paz Wipf group- Current Literature ctober 8, 2011 Dimas
Introduction to Synthesis: Design (CHE686) Spring 2015 Exam #1 3/6/15
Introduction to ynthesis: Design (CE686) pring 2015 Exam #1 3/6/15 AME: KEY ome Pointers: 1. ELAX!! 2. ead the instructions for each question carefully. Be sure you understand what is required. If you
Convergent Route to ent-kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α6α- Diacetoxy-ent-kaura-9(11),16-dien- 12,15-dione
Convergent Route to ent-kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α6α- Diacetoxy-ent-kaura-9(11),16-dien- 12,15-dione Xiangbo Zhao, Wu Li, Junjie Wang, and Dawei Ma* Shanghai Institute
CEM 852 Exam What is the ratio of (S) / (R) alcohol formed during this reaction? (2 pts) baker's yeast. H 2 O, sucrose 25 C
CEM 852 Exam-1 February 19, 2005 This exam consists of 5 pages. Please write ALL your answers in the answer books. Please write legibly and draw all structures clearly. Good luck. 1. What is the ratio
Total Synthesis of Saxitoxin
Total ynthesis of axitoxin 2 2 2 John Baird April 11, 2006 1 First isolated in 1957 by chantz et al Isolation and Properties X-Ray tructure obtained in 1975 Freely soluble in water and methanol ptical
CEM 852 Final Exam. May 6, 2010
CEM 852 Final Exam May 6, 2010 This exam consists of 7 pages. Please make certain that your exam has all of the necessary pages. Total points possible for this exam are 150. n answering your questions,
CEM 852 Final Exam. May 5, 2011
CEM 852 Final Exam May 5, 2011 This exam consists of 8 pages. Please make certain that your exam has all of the necessary pages. Total points possible for this exam are 150. In answering your questions,
A Concise Synthesis of ( )- Aplyviolene Facilitated by a Stragetegic Ter<ary Radical Conjugate Addi<on
A Concise Synthesis of ( )- Aplyviolene Facilitated by a Stragetegic Ter
CEM 852 Exam-2 April 11, 2015
CEM 852 Exam-2 April 11, 2015 This exam consists of 6 pages. Please make certain that your exam has all of the necessary pages. Total points possible for this exam are 100. In answering your questions,
Synthesis of Substituted 1,4-Dienes by Direct Alkylation of Allylic Alcohols Kolundzic, F.; Micalizio, G. C. J. Am. Chem. Soc. 2007, 129,
Synthesis of Substituted 1,4-Dienes by Direct Alkylation of Allylic Alcohols Kolundzic, F.; Micalizio, G. C. J. Am. Chem. Soc. 2007, 129, 15112-15113. Total Synthesis and Structure Elucidation of (+)-orbasin
A Stereoselective Synthesis of (+)-Gonyautoxin 3
A Stereoselective Synthesis of (+)-Gonyautoxin 3 Mulcahy, J. V.; Du Bois, J. J. Am. Chem. Soc. 2008, 130, 12630-12631 Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via
Studies Toward the Total Synthesis of (±)-Noelaquinone
Research Topic Seminar 18 June 2005 Studies Toward the Total Synthesis of (±)-Noelaquinone David Amantini WIPF GRUP The Role of Natural Products in Drug Discovery For thousands of years medicine and natural
Short Literature 8/9/10
Short Literature 8/9/10 Reiter, M.; Torssell, S.; Lee, S.; MacMillan, D. W. C. The organocatalytic three-step total synthesis of ()-frondosin B Chem. Sci. 2010, 37-42. Spangler, J. E.; Carson, C. A.; Sorensen,
Comparative Synthesis of Ingenol. Tyler W. Wilson SED Group Meeting
Comparative Synthesis of Ingenol Tyler W. Wilson SED Group eting 2.27.07 Ingenol: Biology, Isolation, and istory During WWII a latex was manufactured by precipitating the milky juice of the Euphorbia Ingen
A Highly Convergent and Biomimetic Total Synthesis of Portentol
A ighly Convergent and Biomimetic Total Synthesis of Portentol portentol B. Cheng, D. Trauner, J. Am. Chem. Soc. 2015, 137, 13800 13083 Departement of Chemistry and Center for Integrated Protein Science
Total Synthesis of Callipeltoside A. Denmark Group Meeting Aaron Bailey September 23, 2008
Total Synthesis of Callipeltoside A Denmark Group eting Aaron Bailey September 23, 2008 Callipeltoside A First isolated from Lithistid sponge in 1996 Exhibits moderate cytotoxicity against human bronchopulmonary
Approaches to the Synthesis. of Tetrahydropyrans. (and closely related heterocycles)
Approaches to the Synthesis of Tetrahydropyrans (and closely related heterocycles) William Morris Literature Presentation July 6, 2004 I. Intro A Nomenclature B Prevalence in Nature C Biosynthetic Considerations
Total Synthesis of ( )-Virginiamycin M2
Total Synthesis of ( )-Virginiamycin M2 Jie Wu and James S. Panek, Angewandte Chemie International Edition, 2010, 49, 6165-6168 btained from the CDC Public ealth Image Library. Image credit: CDC/Dr. David
Total Syntheses of Manzamine A.
Total yntheses of Manzamine. R E Winkler, 1998 hv D B R akagawa, 2000 [4+2] B R Me P 2 Me B TBDP Pandit, 1991 [4+2] E manzamine Martin, 1999 [4+2] R Me 2 B R R Ramil Baiazitov. ED group meeting. February
Total Syntheses of Minfiensine
Total Syntheses of Minfiensine Douany, A. B.; umphreys, P. G.; verman, L. E.*; Wrobelski, A. D., J. Am. Chem. Soc. 2008, ASAP. D: 10.1021/ja800163v Shen, L.; Zhang, M.; Wu, Y.; Qin, Y.*, Angew. Chem. nt.
Synthetic Organic Chemistry Final Exam Resit (6KM33) Thursday, 26th June, 2014, 9:00 12:00 (3 h)
Synthetic rganic Chemistry Final Exam Resit (6KM33) Thursday, 26th June, 2014, 9:00 12:00 (3 h) This is an open-book written exam. The course textbooks (Warren & Wyatt, 2 nd Ed.) with personal notes and
Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide
61.7 g prepared in 39 steps 43 chemists worked on the project which lasted 20 months Chris Kendall @ Wipf Group 1 3/27/04 8 22 1 5 24 carbon linear polypropionate chain containing stereocenters (6 hydroxyl
Synthesis of the Phomoidrides (CP 225,917 & CP 263,114) Chem. Rev. 2003, 103, 2691.
ynthesis of the Phomoidrides (P 225,917 & P 263,114) hem. Rev. 2003, 103, 2691. 15 7 26 2 7 16 14 1 2 5 7 2 7 1 2 1 4 2 6 1 5 9 1 7 1 9 2 9 1 5 (+)-P hom oidr ide A ; 7 = (P- 225,917) (+)-P hom oidr ide
Studies toward the Synthesis of Azadirachtin: Total Synthesis of a Fully Functionalized ABC Framework and Coupling with a Norbornene Domain
Studies toward the Synthesis of Azadirachtin: Total Synthesis of a Fully Functionalized ABC Framework and Coupling with a Norbornene Domain Nicolaou and Co-workers Angew. Chem. Int. Ed. 2005, 44, 3443
JACS 1982: A Survey of Papers with a Focus on Synthetic Organic Chemistry
JAC 1982: A urvey of Papers with a Focus on ynthetic rganic Chemistry Baran Lab Group eting 15 ctober 2003 Carlos A. Guerrero eagents and thods 1 2 [] 2 2 1 1 PhC, Et 3 2 [] 2 1 2 1 By 1982, the [3 + 2]
The Amphidinolide T-Series
How a Total ynthesis Evolves ver Time The Amphidinolide T-eries H Jason M. tevens 12/06/2006 Amphidinolide Natural Products Isolated in 2000 from marine dinoflagellates of the genus Amphidinium living
Synthesis of Amphidinolide X and an Exploration of Key Reactions
PJM 1/12/05 Synthesis of Amphidinolide X and an Exploration of Key eactions Lepage,.; Kattnig, E.; Furstner, A. JACS, 2004, 126, 15970-15971. 7 13 1 6 19 - Produced by marine dinoflagellates, Amphidinium
Baran Group Meeting 04/07/04 The Total Synthesis of (+)-Ryanodol
Baran Group eting 04/07/04 The Total Synthesis of ()-Ryanodol A. Bélanger; D. Berney;. Borschber; R. Brousseau; A. Doutheau; R. Durand;. Katayama; R. Lapalme; D. Leturc; C. Liao; F. MacLachlan; J. Maffrand;
CHEM 330. Topics Discussed on Oct 5. Irreversible nature of the reaction of carbonyl enolates with the electrophiles discussed on Oct 2
CEM 330 Topics Discussed on ct 5 Irreversible nature of the reaction of carbonyl enolates with the electrophiles discussed on ct 2 Kinetic control in an irreversible reaction: the product that is obtained
total synthesis of diospongin A, B and their enantiomers, b) towards the enantioselective total
ABSTRACT Thesis title: Enantioselective total synthesis of diospongins, towards the enantioselective total synthesis of solandelactones and an expedient synthesis of eantioenriched substituted (benzofuran-yl)
Reactivity Umpolung-1 Ready
eactivity Umpolung-1 eady eactivity Umpolung: reversal of normal polarity electrophiles become nucleophiles nucleophiles become electrophiles complimentary disconnections ormal reactivity: x = heteroatom
Problem Session(5) Please provide each reaction mechanisms and explain the stereoselectivities.
Problem ession(5) Please provide each reaction mechanisms and explain the stereoselectivities. 2017.10.28. iroaki Matoba Boc 1.BF 3 Et 2,C 2 Cl 2,-78 C; allyltm,-78to-20 C 2.MsCl,Et 3,C 2 Cl 2,0 Ctort
Syntheses of Leucascandrolide A. Supergroup Meeting August 4 th, 2004 Yu Yuan
Syntheses of Leucascandrolide A Supergroup Meeting August 4 th, 2004 Yu Yuan Leucascandrolide A Me Me Me Dambrosio, M.; Guerriero, A.; Debitus, C.; Pietra, F. elvetica Chimica Acta 1996, 79, 51-60 Me 1
Supporting Information
upporting Information Unified Total ynthesis of Pteriatoxins and their Diastereomers Fumiyoshi Matsuura, René Peters, Masahiro Anada, cott. arried, Junliang ao and Yoshito Kishi* Department of Chemistry
CuI CuI eage lic R tal ome rgan gbr ommon
Common rganometallic eagents Li Et 2 Li Mg Et 2 Li alkyllithium rignard Mg Mg Li Zn TF ZnCl 2 TF dialkylzinc Zn 2 2 Zn Li CuI TF ganocuprate CuI 2 2 CuI common electrophile pairings ' Cl ' '' ' ' ' ' '
Stereoselective reactions of enolates
1 Stereoselective reactions of enolates Chiral auxiliaries are frequently used to allow diastereoselective enolate reactions Possibly the most extensively studied are the Evan s oxazolidinones These are
Stereoselective reactions of enolates: auxiliaries
1 Stereoselective reactions of enolates: auxiliaries Chiral auxiliaries are frequently used to allow diastereoselective enolate reactions Possibly the most extensively studied are the Evan s oxazolidinones
JACS ASAP Article: Published 3/12/08. Lei Jiao, Changxia Yuan and Zhi-Xiang Yu. Current Literature: 3/29/08. David Arnold
Tandem h(i)-catalyzed [(5+2)+1] Cycloaddition/Aldol eaction for the Construction of Linear Triquinane Skeleton: Total Syntheses of (+)-irsutene and (+)-1- Desoxyhypnophilin JACS ASAP Article: Published
The aldol reaction with metal enolates proceeds by a chair-like, pericyclic process: favored. disfavored. favored. disfavored
The aldol reaction with metal enolates proceeds by a chair-like, pericyclic process: Z-enolates: M 2 M 2 syn 2 C 2 favored 2 M 2 anti disfavored E-enolates: M 2 2 C 3 C 3 C 2 favored 2 M M disfavored In
Protecting Groups in Organic Synthesis-1 Ready
Protecting Groups in rganic Synthesis-1 eady Protecting Groups for Alcohols Protecting groups are a sad fact of synthetic chemistry They are usually needed, but rarely desired Many syntheses have stalled
Classics in Tetrahedron Letters
Classics in Tetrahedron Letters Jeremy Richter Baran Group Meeting: 9/24/03 The Plan Methodology Protecting Groups atural Products Syntheses Methodology xidation of Vicinal Diols R R' R'' 1. Cl 2, DMS,
Synthesis of Resorcinylic Macrolides
Synthesis of Resorcinylic Macrolides X H H H H Cl X= Radicicol (1) X= CH2 Cycloproparadicicol (2) Danishefsky, S. J. J. Am. Chem. Soc. 2004, 126, ASAP Danishefsky, S. J. rg. Lett. 2004, 6, 413-416 Danishefsky,
Prof. Ang Li. Literature Seminar Kosuke Minagawa (D2)
Prof. Ang Li Literature Seminar 2017. 10. 28 Kosuke Minagawa (D2) 1 2 3 aspidodasycarpine 1) 2 C sespenine 3) atural Products Synthesized by Ang Li group clostrubin 6) drimentine A 7) i-bu rubriflordilactone
A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones without High Dilution or Slow Addition
A ew Strategy for Efficient Synthesis of Medium and Large ing Lactones without High Dilution or Slow Addition BF 3 Et 2 TIPS 2,4,6-collidine n + n+2 ' ' Zhao, W.; Li, Z; Sun, J. J. Am. Chem. Soc. 2013
JOC: 1985 Year in Review
Baran Group eting JC: 1985 Year in eview Syntheses discussed: thodoligies discussed: Quadrone 2 C (+)-irsutic Acid C (±) Coriolin (!)-Longifolene (!)-astanecine Manganese (III)-mediated "-lactone annulation
Total Synthesis towards Maoecrystal V
Total Synthesis towards Maoecrystal V isolated from the leaves of a Chinese medicinal herb, Isodon eriocalyx in 2004. structure was determined by comprehensive NMR and MS spectroscopic analysis and confirmed
I. Liu Lab. Ka<e Boknevitz 1
A ighly Convergent Total Synthesis of Leustroducsin B Barry M. Trost,* Berenger Biannic, Cheyenne S. Brindle, B. Michael Keefe, Thomas J. unger, and Ming-Yu gai Department of Chemistry, Stanford University,
Guideline 5: Tactical Bonds
Guideline 5: Tactical Bonds f the molecule contains more than one functional group and hence there is a choice of which bonds to disconnect, how do you decide? Practice, but here are a few rough guidelines
Protecting Groups. Tactical Considerations
Tactical Considerations Cheap & commercially available Easy & efficient introduction Should not create any stereogenic center Stable throughout reaction, work-up & purification Efficient removal By-products
Highlights in the Progress of Biomimetic Strategies for the Construction of Complex Natural Products. Chris Galliford 26 th August 2003
ighlights in the Progress of Biomimetic Strategies for the Construction of Complex Natural Products Chris Galliford 26 th August 2003 The Biomimetic Approach Inspiration for biomimetic synthesis of a target
I. Introduction. II. Retrosynthetic Analysis. Andrew Baggett. Liu lab
Total Synthesis of Limonin Shuji Yamashita,* Akito Naruko, Yuki Nakazawa, Le Zhao, Yujiro Hayashi, Masahiro Hirama Tohoku University, Department of Chemistry, Aramaki-aza aoba, Aoba-ku, Sendai 980-8578
Total Synthesis of the Chartellines
Total Synthesis of the Chartellines X Y chartelline A, X = Y = chartelline B, X =, Y = chartelline C, X = Y = Mariam Shamszad ovember 1, 2006 Background Chartellines A, B, and C were isolated in the 1980s
MULTICOMPONENT REACTIONS AND ORGANOCATALYSIS: A SUITABLE COMBINATION FOR STEREOSELECTIVE SYNTHESIS OF HIGHLY SUBSTITUTED BENZAZEPINES
MULTICMPET REACTIS AD RGACATALYSIS: A SUITABLE CMBIATI FR STERESELECTIVE SYTHESIS F HIGHLY SUBSTITUTED BEZAZEPIES Martina Spallarossa Department of Chemistry and Industrial Chemistry, University of Genoa
Total Synthesis of Trioxacarcin DC-45-A2
Total Synthesis of Trioxacarcin DC-45-A2 icolaou, K. C.; Cai, Q.; Qin, B.; Petersen, M. T.; Mikkelsen,. J. T.; eretsch, P. Angew. Chem. nt. Ed. Engl. 205, 54, 3074 3078. D : 0.002/anie.2040369 Valentin
Recent Total Syntheses! Published in Nature!
Recent Total Syntheses! Published in ature! Eric ewcomb 8/21/2011! 2 S 3 2 2 ature Then and ow! First published ov. 4th, 1869 First issue states two objectives: 'The objective which it is proposed to attain
VINBLASTINE. H MeO 2 C MeO. OAc. CO 2 Me. Me H
VIBLATIE 2 C 1 C 2 Ac a 3: catharanthine C 2 Ac C 2 2: ( )-vindoline xidation 5' 2 C 3' 16' 20' Ac C 2 1: (+)-vinblastine b 4 C 2 TFAA, -50 C Polonovski fragmentation 6' 5' 16' C 2 5 TFA 4' 3' 15' 16'
Enolates: Z(O,R) (O,R)- and E(O,R) (O,R)-enolates
Enolates: Z(,) (,)- and E(,) (,)-enolates egardless of other groups the encircled ' and - determine whether one is Z(,)- or E(,)- enolate. - - ' ' (E)-enolate (Z)-enolate Enolates: deprotonation 90 ' Most
Practice Synthetic Problems: CHEM 235 Page 2
Practice Synthetic Problems: CM 235 Page 2 Syntheses based on diethyl malonate, ethyl acetoacetate, etc. Using diethyl malonate and any other necessary organic reagents, show a synthesis of: a) 2,2-dimethyl-1,3-propanediamine
Synthetic Efforts Toward Palau'amine
ynthetic Efforts Toward Palau'amine Doug Behenna, Ryan McFadden Eric Ashley, Jenn tockdill Akihiko Iwashita August 9, 2004 2 2 2 Isolation of Palau'amine and Congeners R 2 R 1 R 1 R 2 2 2 2 2 2 2 R 1 =
Approaches to the Synthesis of Macquarimicins and Cochleamycins
Ac Macquarimicin A Cochleamycin A Approaches to the Synthesis of Macquarimicins and Cochleamycins Drew Adams Friday Seminar March 18, 2005 Isolation and Activity Ac Isolated in 1995 from Micromonospora
Literature Report 3. Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A. Date :
Literature Report 3 Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A Reporter : Xiao-Yong Zhai Checker : Shubo u Date : 2017-10-30 Pritchett, B. P.; Donckele, E. J.; Stoltz, B. M. Angew.
Massachusetts Institute of Technology Organic Chemistry Problem Set 1. Functional Group Transformations Study Guide
Massachusetts Institute of Technology rganic Chemistry 5.511 Problem Set 1 September, 2007 Prof. Rick L. Danheiser Functional Group Transformations Study Guide The purpose of this three-part study guide
R or S? oxidation #: hybridization:
Remember Lone pair-assisted ionization. ame 15 F07-Exam o. 1 Page I. (0 points) The following compounds are those used in our study on the enzymatic transformation of cholesterol to pregnenolone. 1) Designate
Electrophilic Carbenes
Electrophilic Carbenes The reaction of so-called stabilized diazo compounds with late transition metals produces a metal carbene intermediate that is electrophilic. The most common catalysts are Cu(I)
Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis
Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis C 3 C3 Liffert, R., Linden, A., Gademann, K. J. Am. Chem. Soc. 2017, 139, 16096 Presented by: Brendyn Smith CEM 852
Total Synthesis of (-)-Mersicarpine
Total Synthesis of (-)-Mersicarpine Rie akajima, Tsuyoshi gino, Satoshi Yokoshima, and Tohru Fukuyama. J. Am. Chem. Soc. ASAP Published online 1-7-2010 Eric E. Buck Current Literature January 23, 2010
Memory of Chirality: A Strategy for Asymmetric Synthesis
Memory of Chirality: A trategy for Asymmetric ynthesis David J. Richard eptember 14, 2005 Two Forms of Chirality Absolute (tatic) Chirality 2 - Absolute chirality - orientation of functional groups at
A Unified Strategy to ent-kauranoid Natural Products: Total Syntheses of ( )-Trichorabdal A and ( )-Longikaurin E
A Unified Strategy to ent-kauranoid Natural Products: Total Syntheses of ( )-Trichorabdal A and ( )-Longikaurin E John T. S. Yeoman, Victor W. Mak, and Sarah E. Reisman. J. Am. Chem. Soc. 2013, 135, 11764.
11-Step Enantioselective Synthesis of ( )-Lomaiviticin Aglycon
11-Step Enantioselective Synthesis of ( )-Lomaiviticin Aglycon Seth B. erzon, Liang Lu, Christina M. Woo, and Shivajirao L. Gholap J. Am. Chem. Soc. ASAP DI 10.1021/ja200034b Melissa Sprachman Current
Nine-Step Enantioselective Total Synthesis of (+)-Minfiensine
ine-step nantioselective Total Synthesis of (+)-Minfiensine Jones, S. B.; Simmons, B.; MacMillan, D. W. C.* J. Am. Chem. Soc. 2009, ASAP. DI: 10.1021/ja906472m Kara George Wipf Group - Current Literature
Total Synthesis of the Proposed Structure of Briarellin J
Total Synthesis of the Proposed Structure of Briarellin J Michael T. Crimmins, Mark C. Mans, and Abimael D. Rodríguez. rg. Lett. 2010, ASAP Ac Ac originally proposed structure revised structure Eric E.
Short Lit
Short Lit. - 7-12-2010 Jonathan A. Brekan a Department of Chemistry, orthwestern University, 2145 Sheridan Road, 60208, Evanston, Illinois, United States of America Citronellal Monoterpenoid distillate
Ladderanes: Uses and Synthesis. Nicholas Anderson Denmark Group Meeting October 28, 2008
Ladderanes: Uses and Synthesis icholas Anderson Denmark Group Meeting ctober 28, 2008 utline Ladderane types and classifications Potential applications of ladderanes Synthesis of ladderanes Ladderane natural
Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes
Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes I. Introduction Cembranes are a large class of macrocyclic diterpenes (C 20) isolated from a diverse group of organisms (both plants and animals)
ROC Exam Problem 1
RC Exam 2012 Problem 1 Silyl ether 1 is transformed into 2 in a two step process. Predict, through a detailed mechanistic rationale, the stereochemistry of the newly formed chiral center. TBS Si 1) Ms
C 13 -C 14 C CHO. CrCl 2, Ni(COD) 2 4Å mol sieves. NHK reaction. nbuli HN(TMS) 2. aldol reaction
Introduction to Synthesis: Design (E 66) Spring 2015 Problem Set #2 KEY 1. The Evans synthesis of (+)-discodermolide appears in the Ph.D. thesis of David alstead (arvard, 1999). copy of this work is posted
Chemistry 35 Exam 2 Answers - April 9, 2007
Chemistry 35 Exam 2 Answers - April 9, 2007 Problem 1. (14 points) Provide the products for the reactions shown below. If stereochemistry is important, be sure to indicate stereochemistry clearly. If no
An Analysis of the Total Syntheses of Aphidicolin
An Analysis of the Total Syntheses of Aphidicolin An Evans Group Afternoon Seminar Krista Beaver March 20, 1998 A B D C Aphidicolin Isolated from the fungus Cephalosporium aphidicola (esp, Chem. Comm.1972,
Total Synthesis of (-)-Anominine
Total Synthesis of (-)-Anominine Ben Bradshaw, Gorka Etxbarria-Jardí and Josep Bonjoch* Laboratori de Química rgànica, Facultat de Farmàci, Universitat de Barcelona, Barcelona, Spain J. Am. Chem. Soc.
Back to Sugars: Enzymatic Synthesis
Back to Sugars: Enzymatic Synthesis Zhensheng Ding ov. 04 orthrup, A. B.; M acm illan, D. W. C. Science 2004, 305, 1752 orthrup, A. B. and MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 6798-6799 orthrup,
A Review of Total Synthesis of Spirotryprostatin A and B. Jinglong Chen Supergroup meeting Princeton University June
A Review of Total Synthesis of Spirotryprostatin A and B Jinglong Chen Supergroup meeting Princeton University June 28 2006 ovel Mammalian Cell Cycle Inhibitors, Spirotryprostatins A and B Me Spirotryprostatin
Towards Maoecrystal V: A Comparison of Recent Strategies
Towards Maoecrystal V: A Comparison of Recent Strategies Reactant/Reagent Current Literature: November 14, 2009 lissa Sprachman lissa Sprachman @ Wipf Group Page 1 of 14 12/28/2009 Maoecrystal V: Structural
Use of the non-aldol aldol process in the synthesis of the C1 C11 fragment of the tedanolides: use of lactol ethers in place of tetrahydrofurans
Pergamon Tetrahedron Letters 41 (2000) 9719 9723 TETRAHEDRON LETTERS Use of the non-aldol aldol process in the synthesis of the C1 C11 fragment of the tedanolides: use of lactol ethers in place of tetrahydrofurans
Total Synthesis of Cyclosporine: Access to N-Methylated Peptides via Isonitrile Coupling Reactions
Total Synthesis of Cyclosporine: Access to -thylated Peptides via Isonitrile Coupling Reactions Xiangyang Wu, Jennifer L. Stockdill, Ping Wang, Samuel J. Danishefsky* J. Am. Chem. Soc. 2010,132, 4098-4100
Enantioselective Total Synthesis of (-)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine
Enantioselective Total Synthesis of (-)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine Julian A. Codelli, Angela L. A. Puchlopek, and Sarah E. Reisman* JACS. ASAP. ct. 24, 2011 DI: 10.1021/ja209354e
"-Amino Acids: Function and Synthesis
"-Amino Acids: Function and Synthesis # Conformations of "-Peptides # Biological Significance # Asymmetric Synthesis Sean Brown MacMillan Group eting ovember 14, 2001 Lead eferences: Cheng,. P.; Gellman,
Suggested solutions for Chapter 27
uggested solutions for Chapter 27 27 PRBLEM 1 uggest a mechanism for this reaction, commenting on the selectivity and the stereochemistry. Me 2 1. t-buk 2. Raney Ni Et The opportunity to explore the consequences
CHEM 330. Final Exam December 5, 2014 ANSWERS. This a closed-notes, closed-book exam. The use of molecular models is allowed
CEM 330 Final Exam December 5, 2014 Your name: ASWERS This a closed-notes, closed-book exam The use of molecular models is allowed This exam consists of 12 pages Time: 2h 30 min 1. / 30 2. / 30 3. / 30
Asymmetric Nucleophilic Catalysis
Asymmetric ucleophilic Catalysis Chiral catalyst X 2 Chiral catalyst X = alkyl, X 1 2 1 Vedejs, E.; Daugulis,. J. Am. Chem. Soc. 2003, 125, 4166-4173 Shaw, S. A.; Aleman,.; Vedejs, E. J. Am. Chem. Soc.
Dr. P. Wipf Page 1 of 5 10/7/2009. Cl Ru. Kingsbury, J. S.; Harrity, J. P. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791.
Dr. P. Wipf Page 1 of 5 10/7/2009 Alkene Metathesis Grubbs II published The Catalysts Me Mo F 3C CF3 Me F 3C CF3 C(Me) 2 chrock, R. R.; Murdzek, J..; Bazan, G. C.; Robbins, J.; DiMare, M.; 'Reagan, M.
Total synthesis of Spongistatin
Literature Semminar 1. Introduction: Total synthesis of Spongistatin Chen Zhihua (M2) Isolation: Pettit et al. J. rg. Chem. 1993, 58, 1302. Kitagawa et al. Tetrahedron Lett. 1993, 34, 1993. Fusetani et