Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes

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1 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) They are especially abundant in marine environments and often possess interesting biological profiles (defense mechanisms) Gorgonian corals produce a large number of cyclized and oxidized cembranes which can grouped into four main categories: (1) Cladiellin = eunicellin (2) Briarellin (3) Asbestinin () Sarcodictyins The Classification largely rests on the type of ether linkage, thus leading to various ring-systems (although some possess no ether linkages) bond-forming event [] [] Cembrane skeleton Within each Class there is also a large variation in oxygenation patterns: (ot all positions are simultaneously oxidized) Cladiellins [] Cladiellins largest group Briarellins 1,2 Shift? Detailed biosynthetic studies have not been performed Sarcodictyins Asbestinins Sites of oxygenation in the Cladiellins Some oddities worth noting: C C Briarellin oxygenation sites Asbestinin oxygenation sites Sarcodictyin oxygenation ring-opened briarellin ring-opened asbestinin for excellent reviews see: Bernardelli, P., Paquette, L.A. eterocycles. 1998, 9, Sung, P-J., Chen, M-C. eterocycles. 2002, 57,

2 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes Ac Ac Ac Ac Ac Ac Ac solenopodin A solenopodin B Ac solenopodin C Ac solenopodin D Ac 6-Acetoxycladiella 7(16),11-dien-3-ol CPr Cladiell-11-ene- 3,6,7-triol PrC CPr 12,13-Diacetoxycladiella- 2,6-dien-11-ol o ame Labiatin A alcyonin (revised) Litophynin A Ac Litophynin B Cladiella-6,11- dien-3-ol Ac 3-Acetoxycladiell- 11-ene-6,7-diol Ac 3-Acetoxycladiella- 6,11-diene Cladiellin Ac Litophynin C Litophynin I monoacetate CPr CPr Sclerophytin F, A (revised) Ac Litophynin J CPr Sclerophytin B (revised) CPr Litophynin Ac Ac CPr Litophynin I CPr Litophynin D 2

3 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes 3 Ac Ac Ac Ac Ac Ac Ac Labiatin C labiatamide A CPr Ac PrC 12-Acetoxy-3,13- dibutanoyloxycladiell- 6-ene-,11-diol Ac Ac Calicophirin B Ac Ac Ac Ac Ac 3,6-Diacetoxy-11,12- epoxycladiellan-7-ol Ac Ac (6E)-11-Acetoxycladiellin Ac Ac (6Z)-11-Acetoxycladiellin Ac Ac Ac labiatamide B Ac Palmonine C Ac Ac Palmonine A Ac Ac Palmonine F Ac Ac Ac Palmonine B Ac Ac Palmonine D Ac Ac Palmonine E Cladiellane-3,7,11- triol Ac 11-Acetoxycladiellane-3,7-diol vigulariol polyanthellin A Ac Ac Ac Ac massileunicellin-a Ac massileunicellin-d Ac Ac Ac Ac Ac massileunicellin-b Ac Ac Ac massileunicellin-c Ac Ac Ac Ac Ac unamed eunicellin

4 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes Sclerophytin F CPr 3-Butanoyloxycladiell- 11 (17)-ene-6,7-diol Ac Sclerophytin E Ac Ac Ac Ac astrogorgin Ac Ac Ac phirin Ac 6-Acetoxycladiell-11 (17)-ene-3,7-diol Sclerophytin F methyl ether Et Et Patagonicol Ac 3-Acetoxy-6-(3- methylbutanoyloxy) cladiell-11 (17)-en- 7-ol CPr Litophynin E Sclerophytin D Ac Sclerophytin C CPr Litophynol B cladiellisin Ac 3-Acetoxycladiella- 7(16), 11(17)-dien- 6-ol CPr Litophynin F cladiellaperoxide CPr Litophynol A CPr Litophynin G Ac 3-Acetoxycladiell- 11(17)-en-6-ones Ac Ac (6Z)-3,13,18- Triacetoxycladiella- 6,11-diene Ac Ac Eunicellin Ac Ac Ac Ac Ac Calicophirin A Ac Ac Ac Labiatin B

5 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes Ac Ac Ac Ac Ac Ac Ac Ac AcAc Ac Ac Ac Ac Ac Ac Ac unamed eunicellin unamed eunicellin unamed eunicellin unamed eunicellin Briarellin C CPr 2 CC 7 15 Briarellin D Ac Ac Ac C 7 15 C 2 C 7 15 C 2 Ac unamed eunicellin Briarellin G Briarellin I Ac Ac Ac Ac unamed eunicellin Briarellin seco-briarellin I CC 7 15 C C 2 CC 7 15 Briarellin A tentative Ac Briarellin J peroxy Briarellin L Briarellin B Ac Briarellin K Ac peroxy Briarellin K 2 CC 7 15 C Briarellin E Briarellin L Ac Briarellin M 2 CC 7 15 Ac C Briarellin F 2 CC 7 15 deacetyl-briarellin L Ac Briarellin 5

6 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes C 3 7 C C 3 7 C Ac CPr CPr Ac Briarellin Ac 11-Acetoxy-- deoxyasbestinin D 11-Acetoxy-- deoxyasbestinin E Ac seco-asbestinin Ac C PrC Briarellin P -deoxyasbestinin C Ac 11-Acetoxy-- deoxyasbestinin F Ac Asbestinin-12 Ac 11-Acetoxy-- deoxyasbestinin B Ac Asbestinin-6 Ac Asbestinin-11 Ac Asbestinin -13 CC 7 15 CC 7 15 CC 7 15 PrC 2 -Deoxyasbestinin A CPr Asbestinin-3 Asbestinin-2 Ac Asbestinin -1 Ac CC 5 11 PrC Asbestinin-1 Ac -Deoxyasbestinin G PrC 2 Asbestinin epoxide PrC 2 Asbestinin-5 Ac Ac Asbestinin-8 PrC 2 Ac Ac Asbestinin -17 Asbestinin-5 acetate CC 7 15 Ac Ac Ac 6

7 Ac Asbestinin-7 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes CC 7 15 Ac Asbestinin-15 Ac Ac Asbestinin-19 Ac Ac Asbestinin-16 CC 7 15 PrC Asbestinin-9 Ac Asbestinin-10 PrC Ac Ac Ac PrC Ac Asbestinin- Ac C 2 Sarcodictyin A Asbestinin-20 C 2 Et Sarcodictyin B Asbestinin-18 CC 7 15 C 2 Sarcodictyin C Asbestinin-21 imid Ac Sarcodictyin D C 2 Asbestinin-22 imid Valdivone A Asbestinin-23 Valdivone A methoxyketal C 2 Sarcodictyin F C 2 Et Sarcodictyin E Valdivone B Valdivone B methoxyketal Dihydrovaldivone A 7

8 Cladiellin, Briarellin, Asbestinin & Sarcodictyin Diterpenes Ac eleuthoside A Ac Ac eleuthoside B Ac Ac Eleutherobin 8

9 Cladiellins ( )-7-deacetoxyalcyonin acetate (1995) (S)-carvone verman 1) 2, Pt 2 Ac 2) LDA, Ph(Tf) 2 3) Pd(PPh 3 ), IS ( 3 Sn) 2 78% 1 2 The Prins-Pinacol eaction acid (- 2 ) 2 1 Prins (via chair TS) prepared in 2 steps 1) i. t-buli, TF, -78 C ii. C I MP TMS TIPS TMS BF 2) PPTS, 3 Et 2, C 2 Cl 2 6% -55 C -20 C 1 prepared in steps from 2 (9:1 dr) 79% 3 (S)-glycidyl pivalate 2 1 C Pinacol formyl TF TMS TIPS Single Isomer! 2 F 3 B 1 favored 2 F 3 B 1 2 C 1 1) Ac, 2 2) hν, hexanes 71% TMS 1 BF 3 2 X 1 BF 3 2 C 1 2 Stereochemical Model for the Prins-Pinacol earrangement MacMillan, D.W.C., verman, L.E. J. Am. Chem. Soc. 1995, 117,

10 Cladiellins ( )-7-deacetoxyalcyonin acetate (1995) verman Ac 1 TMS 1) SAE 2) edal, 2 79% 2 1) PvCl, pyr. 2) TBSTf, lutidine 3) B-I-9-BB, AC ) i-bu 2 Al 5) TPAP, M 78% 3 I TBS 1) Ph 3 P=C TF, -30 C 2) Tf, i-pr 77% A streamlined route was also developed (see JACS full paper) Ac 1) Ac 2 2) n-bu F 88% TBS icl 2 -CrCl 2 DMS 65% (>20:1 dr) I TBS 5 3 Sclerophytin A (Proposed)? Sclerophytin A (evised) Paquette and verman groups ( ) A Sclerophytin A as drawn in the isolation paper ( and S not denoted) S B presumably the structure they meant to depict in the isolation paper C B's actual conformation, however would corrrespond to C (Paquette's depiction) D vermans depiction of C (same structure) "Particularly enigmatic to us was the manner in which the isolation group depicted the configuration at C-3 in their formulation. Unfortunately, the intentions behind the use of an "inverted carbon" symbolism here will never be known." L. A. Paquette Paquette, L.A., Moradei,.M., Bernardelli, P., Lange, T. rg. Lett. 2000, 2, Gallou, F., MacMillan, D.W.C., verman, L.E., Paquette, L.A., Pennington, L.D., Yang, J. rg. Lett. 2001, 3, verman, L.E., Pennington, L.D. rg. Lett. 2000, 2, Paquette et. al. J. Am. Chem. Soc. 2001, 123, MacMillan, D.W.C., verman, L. E., Pennington, L.D. J. Am. Chem. Soc. 2001, 123,

11 Cladiellins? Sclerophytin A (evised) Paquette and verman groups ( ) In addition: Cladiellin BF 3 Et 2 Et 2 0 C eported by Faulkner in 1980 An intramolecular etherification produces this sterochemistry This is known to be -config in all the atural products Thus Both the verman and Paquette Groups Target C C Paquette's route to C: n TMS 1) Ph, Δ 2) TMSTf, lutidine n 1) ab, CeCl 3 2) TBDPSCl, imid TBDPS 1) Dibal- TBDPS 3) Py CSA, 2 2) Ac 2, Et 3 ) allylbromide, In 3) TMSC, BF 3 Et 2 TBAB ) KtBu, tbu C 1 (dr = 13:1) (38% 6 steps) 2 78% 3 1) 2, PdCl 2, CuCl, 2 2) CeCl 3 TBDPS Bz 7 1) LMDS, TMSCl; C, Yb(Tf) 3 2) TBDPSCl 3) i-prmgcl, CuBr DMS MPA Bz 6 1) Li TBDPS 2) K, BzCl 3)TBAF )TPAP, M 5 1) Cl TBDPS Cp 2 Ti Al 2 2) abf, Ph, Δ MgBr 3) a, ) Cl 3 C 6 2 CCl, Et 3, DMAP 5% 11

12 Cladiellins Sclerophytin A (Proposed)? Sclerophytin A (evised) Paquette and verman groups ( ) TBDPS Bz 7 1) ab, CeCl 3 2) (Im) 2 C=S 3) Bu 3 Sn, AIB, toluene, 100 C ) DIBAL 68% TBDPS g(ccf 3 ) 2, DMF; 2, ab 5% TBDPS 8 9 1) TPAP, M 2) DIBAL (+ 18% TF ring) 1) Ac 2 2) TBAF 3)o-itroPhenylselenocyanide, Bu 3 P; 2 2 ) DIBAL epi-c ot Sclerophytin C ot Sclerophytin TIPS epi-c ot Sclerophytin TMS C p-ts 2 MgS, C 2 Cl 2-20*C 76% C ot Sclerophytin TMS 10 TIPS hν, Ac p-xylene 2-propanol rt 80% ratio of C:1 = :1 SnCl (10%) 1:1 C 2 Cl 2 / 2-50 C 88% 1 C TMS 1) hν, dioxane 2) TBAF C 3) (t-bu) 3 Al TIPS t-bu 2 Ph -20 C 11 (6.6:1 dr) 12 1% g(ac) 2, TF; ab, a 66% bsm 13 steps TMS TIPS 12

13 Cladiellins Sclerophytin A (Proposed)? Sclerophytin A (evised) Paquette and verman groups ( ) After thoroughly re-evaluating M and MS data, the Paquette lab proposes the following: sclerophytin A identical to previously reported sclerophytin F In a joint publication, using mostly chemistry we have discussed, both the verman and Paquette labs verify the new proposal. The following compounds are prepared sclerophytin A The verman lab also revises the structure of alcyonin sclerophytin B Ac Cladiell-11-ene- 3,6,7-triol proposed revised Friedrich, D., Doskotch,. W., Paquette, L.A. rg. Lett. 2000, 2, Corminboeuf,., verman, L.E., Pennington, L.D. rg. Lett. 2003,

14 Briarellins Briarellin F Briarellin E (S)-Carvone 1) i. 9-BB (2.2 equiv), TF, 0 C ii. a, 2 2, rt -> reflux 2) TEMP, CS, n-bucl, CCl 3 :ac 3 :K 2 C 3 (2:1:1) 58% 1 1) LDA, TF, -78 C; TMSCl, -78 C > 0 C; Ac, 0 C > rt 2) LiAl 78% verman et al. TIPS 5 Ac Ac 1) TFA, Ph, 0 C; 2, rt 2) Ac 2 86% TIPS Ac steps TIPS 3 1) TIPSCl, imid 2) PCC 87% (20:1 dr) 2 1) m-cpba, 0 C 2) TBAF 3) Tf 2, 2,6-lutidine 6 5% Ac Ac 1) 2 S, 2 2) MsCl, Et 3 ; LiAl 3) Bu 8 Sn Cl 2, isopropenyl acetate ) C 7 15 CCl, pyr. 5) Bu 3 SnAlEt 2, CuC 6) I 2 35% I Ac CC ) (t-bu) 2 ()SnCl, 2) DMP 3) CrCl 2 -icl 2 DMS-DMS 59% Briarellin E 1) DMP 79% Briarellin F Corminboeuf,., verman, L.E., Pennington, L.D. J. Am. Chem. Soc. 2003, 123,

15 Cladiellins deacetoxyalcyonin acetate Molander et al. 1) m-cpba 2) 3, DMS 3% Ac 7 Ac α-phellandrene 1) CrCl 2, icl 2 DMF 2) DEAD, Bz PP 3 Cl 3) a, ) Ac 2, pyr. DMAP 62% Et 3 25% 6 TES Ac, hν TES 86% TiCl Ac -80 C 3-80% Tf C 1) Br, t-buli then CuBr DMS then Comins reag. 2) TF/1 Cl 71% 5 1) K, TBSCl 2) PhSeCl; then m-cpba 71% C 2 1) n-buli (2.2 eq.), LiCl; I 2) LiCl, 2, DMS, 130 C 50% Ac 1) WCl 6, n-buli 2) TBSTf, KMDS Ac 1) Ph 3 PC 2 Br, t-buk; 1 Cl Ac Li Ac 8 TBS 57% Yb(Tf) 3 66% BSM Molander, G.A., St. Jean, D.J.Jr., aas, J. J. Am. Chem. Soc. 200, 126,

16 Cladiellins Ac Ac Ac astrogorgin Ac Ac Crimmins et al. Ac Ac ophirin B The Crimmins lab has significant experience in the construction of medium-sized ether ring natural products Br isolaurallene (completed) C Br Br obtusenyne (completed) Cl Thus we will see a unique approach to the eunicellin natural products wherein the 9-membered ether is the key synthetic fragment. Bn (S)-benzyl glycidyl 1) TMSI, n-buli 2) a, PMBCl Bn 3) g(ac) 2, 2 ; PdCl 2, LiCl, CuCl 2, 2 79% PMB PMB 1) MgBr Bn 2) a, BnBr Bn 87% 1 2 (single isomer) 1), Cl 2) a, BrC 2 C 2 3) 3 CCCl, Et 3, then Bn Bn 3 1)aMDS, 3:1 E : Z Bn TES 2 C 7 1) DMP TP 2) Ph 3 P=CC 2 3) TESTf ) PPTS, 5) DMP 6) Ph 3 PC 2 BnCl, t-buk 6 1) DMP 2) Ph 3 P=C() 2 C 2 Et 3) DIBAL ) DP, PPTS 5) a/ 3 Bn Bn Grubb's II Ph 80 C 89% > 15:1 ether/dimer Bn I 2) LiB, Bn 5 Studies Showed that the Dimer is the kinetic product, but is converted (irreversibly) to the ether at higher temperatures Crimmins, M.T., Brown, B.. J. Am. Chem. Soc. 200, 126, Crimmins, M.T., Brown, B.., Plake,.. J. Am. Chem. Soc. 2006, 128, Crimmins, M.T., Ellis, M.J. J. Am. Chem. Soc. 2005, 127,

17 Cladiellins, Asbestinins Bn 2 C TES Z-7 1:3 hν Bn 2 C PhSSPh (cat) (1:1) Crimmins, M.T., Brown, B.. J. Am. Chem. Soc. 200, 126, Crimmins, M.T., Brown, B.., Plake,.. J. Am. Chem. Soc. 2006, 128, TES 7 standing at rt 2 h exo 80% with recycling step Bn Bn To access astrogorgin the following modifications were made: Bn TIPS 1) amds I TIPS Bn 2) LiB To access the asbestinin family: C TBS Bn 110 C Bn C TES Bn 2 C TES 1) MgCl 2) TBAF steps Ac 1) MgCl 2) TBAF Ac 11-acetoxy--deoxyasbestinin D 3) a, naphthalene 1) KMDS, Ac 2 2) Bi(Tf) 3, Ac 2 3) 2, Pd/C ) Ac 2, DMAP Ac Ac Ac Ac TIPS Ac Ac Astrogorgin Ac Ac phirin B 1) TBAF 2) o- 2 PhSeC 3) 2 2 Ac many acetylation conditions Ac Ac Ac 1) TPAP, M 2) ab, CeCl 3 3) Ac 2, DMAP ) TBAF 5) Bi(Tf) 3, Ac 2 17

18 Cladiellins Cladiella-6,11- dien-3-ol TBDPS 5 1) Ph 3 P=C 2 2) TBAF 90% 2 C Tr Tr Ac Polyanthellin Kim et al 1) DIBAL, n-buli 2) n-buli Si 3 then oxalic acid 68% 1) BT, xylenes reflux, 1h 85% Deacetoxy-alcyonin acetate TBDPS C Tr Tr Ac 1) Li, CeCl 3 2) Ac 2, DMAP Et 3 3) K, 18-C-6 t-bu 2 55% Cladiell-11-ene- 3,6,7-triol LMDS, TF 5 C 92% 1) TESTf 2) s, M 2 TBDPS Cladiella-6,11- dien-3-ol 3 As with Crimmins approach, the 9-membered ether is the key piece Cl Tr Bn 1) g(ac) 2, 2 ; Et 3 B, ab 2) Ac 2, DMAP 69% PMB n-butf, Et 3 75% 1) a, ClC 2 C 2 2) Se 2 ; ab 3) PPh 3, CCl TES Ac 62% Polyanthellin TBDPS 1) Ac 2, DMAP 2) Burgess, 70 C 3) TBAF Bn PMB 1 1) ab 2) TBDPSCl, imid 3) trityl bromide, DMAP ) DDQ 69% Tr 2 Ac Deacetoxy-alcyonin acetate Kim,., Lee,., Kim, J., Kim, S., Kim, D. J. Am. Chem. Soc. 2006, 128,

19 Cladiellins (+)-vigulariol C 2 Et 1 prepared in steps from Br(C 2 ) 3 TBS SmI 2, TF, rt 76% C 2 Et 2 single diastereomer! 1. TBSCl, imid. 2. Li, 3. i-bu 2 CCl, Et 3, then C % 3 TBS 2 Cu(CF 3 CCCCF 3 ) 2 5 mol% DCM Δ 96% J. Stephen Clark et al. Et 7 TBS 1. MVK, Ph, Δ 2. K 2 C 3, 58% ( steps) 1. Ph 3 PC 2 Br, t-buk 2. Cl (5% aq.), TF, rt 3. 2, Pt 2. Ph 3 PC 2 58% 8 TBS 1. n-bu F 2. DMP 3. MgCl 75% Et TBS 6 1. amds, PhTf 2 2. Pd(PP 3 ), LiCl Et m-cpba, 0 C 69% SnBu 3 TBS (Z)-5 (+)-vigulariol (5:1) AIB, EtS, Ph, Δ 56% TBS (E)-5 [2,3] TBS Clark, J. S., ayes, S. T., Wilson, C., Gobbi, L. Angew. Chem. Int. Ed ,

20 Sarcodictyins C 2 sarcodictyin A (=) sarcodictyin B (=Et) carvone , a, 2. 2, Pt 2 3. LDA, C 2. TBSCl, Et 3 6% 1 TBS 1. L-Selectride 2. MsCl, Et 3 3. a-naphthalenide 79% 2 TBS 1. C 3 C(Et) 3 n-prc 2 2. DIBAL 72% icolaou et al. 6 PMB 1. C CMgBr 2. TBAF 3. DMP 5 PMB TBS 1. PMBC(=)CCl 3 2. g(ac) 2 3. Li 2 PdCl, CuCl 2 58% TBS 1. (Et) 2 P()C 2 C 2 Et 2. DIBAL 3. Ti(i-Pr), DET, t-bu. MsCl, Et 3 5. a-naphthalenide 71% 3 C TBS 1. CC 2 C 2 Et β-alanine 2. TMSTf 9% PMB TMS 1. DIBAL PMB TMS 1. LMDS PMB 2, Lindlar PMB C 2. TIPSTf 67% C 2 Et 7 8 C TIPS 2. DMP 3. PPTS, 80% 9 TIPS 75% 10 TIPS icolaou, K. C., Xu, J.-Y., Kim, S., hshima, T., osokawa, S., Pfefferkorn, J. J. Am. Chem. Soc. 1997, 119, icolaou, K. C. et al. Angew. Chem. Int. Ed. Engl. 1997, 36, icolaou, K. C. et al. J. Am. Chem. Soc , icolaou, K. C. et al. J. Am. Chem. Soc ,

21 Sarcodictyins PMB TIPS 1. CSA, 2. a, liq. 3 72% TIPS 1. t-bu 2. TBAF 3. DMP. acl 2 5. C CSA, 2 C 2 sarcodictyin A C 2 Et sarcodictyin B a similar approach was used to prepare eleutherobin 1 TES TES C Cl 3 C TMSTf PMB TBS TBS TES TES C PMB TBS TBS steps Ac eleutherobin Also prepared: Ac Ac Ac C 2 Ac S Ac eleuthoside A eleuthoside B Ac dihydro-sarcodictyin A thiazole-eleutherobin epi-eleutherobin 21

22 Sarcodictyins ClCCCl 3 Cl Cl 1) Zn,, Cl 2 1) p-ts 2, 60 C C Ac eleutherobin Danishefsky et al. Li 2% 7 Piv α-phellandrene 1) DMD, 2 C C 2 Cl 2 9% Zn, Et 2, 0 C sonication 65% 6 1 Piv 2) t-bu 60 C 65% 1. CrCl 2, icl 2 DMF 2. PivCl, DMAP 3) TBAF 6% (15:1 dr) 2 5 C 2) TBDPS Br p-ts 2, 2 C 60% 1) i. DIBAL ii. MsCl, pyr. iii. KC, 18-C-6 2) DIBAL 73% (1.3:1 dr) C Li Br 2. TBDPSCl 55% TBDPS Br 8 Piv Ac 2, DMAP -78 C 73% Ac Piv 1. Ag 2, I C 2. KC, Et reflux 3. TBSTf, 2,6-lutidine 9 71% 10 TBS Piv 1) DIBAL 2) TPAP, M 77% TBS 12 Danishefsky et al. Angew. Chem. Int. Ed. 1998, 37, Danishefsky et al. Angew. Chem. Int. Ed. 1998, 37, Danishefsky et al. J. Am. Chem. Soc. 1999, 121,

23 Sarcodictyins TBS i. LDA ii. Comins 80% TBS Tf Pd(PPh 3 ), LiCl Ac Bu 3 Sn 1 50% TBS Ac 1. TBAF 2. esterify 3. PPTS, 38% Ac eleutherobin Piv eleutherobin formal synthesis C. Gennari et al. C s-buli PMP PMP 3. ab. MsCl Cl Ti 5. KC Ph 6. DIBAL Ph 1 Ph 2 3 Ph 1. MMCl, TBAI DIPEA 2. LiBF, 2 MM PMP C Cl Ph Ph s-buli Ti Ph Ph PMP BF 3 Et 2 8 MM PIV 2 TBS Piv 7 CDCl 3 6 MM Piv 1. CA 2. DMP MM PMP PMP Piv 5 kinetically controlled CM (less stable product) 1. PivCl 2. Grubbs II MM PMP PMP Castoldi, D., Caggiano, L., Panigada, L., Sharon.., Costa, A. M., Gennari, C. Angew. Chem. Int. Ed. 2005,,

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.