II: Nomenclature. III: Charcteristics R SH. R S R' sulfide R SOH R S OH HO S O S OH. soft base easily oxidized. thiol. sulfenic acid.

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1 ( ) I Introduction 3 ( 3 ) = 2 Allicin II omenclature 2 thiol ' sulfide oa ysteine Acetyl coenzyme A Adenosyl methionine Gliotoxin &!lactams Lenthionine Mitrasulgynine sulfenic acid sulfinic acid sulfonic acid ' ' sulfoxide sulfone III harcteristics ii. Low affinity to ; trong nucleophilicity pka pka orbital P As 1s 2s 3s e 2p 3p F l Br 3d Et basisity nucleophilicity Et highly polarizable soft base easily oxidized ' l 3 dx 2, dx 2 y 2 dxy, dyz, dxz "! Bulky Et / All 3 DM y. quant i. Less electronegativity compared with xygen Mitragynine

2 iii. Low bond energy ' (89 Kcal) (100 Kcal) v. Electronaccepting conjugative effect iv. Electronreleasing conjugative effect l l 3dxy 2p 2p 3p i. base Ph 3 Ph 2 ii. Br IV Application to the rganic yntheses base l (MTM) ' formation ( 2 ) n BF 3 Et 2, 2 l 2 TM 2 2 TM, ZnI 2, Et 2 ' ' cleavage ( 2 ) n gl 2 or X I or, etc cleavage ( 2 ) n E 2 ' 2 Base E ' ' '

3 PfitznerMoffatt DM, D, (pyridinef 3 ) 2. AlbrightGoldman DMAc wern DM, (F 3 ) 2, Et3, 2 l 2 DM, (l) 2, Et3, 2 l 2 l 4. ParikhDoering DM, 3 pyridine 3 ex.2 ex.1 1. Ph2 2. (Ph) 2 1. Ph Br Ph 1. nbuli 2. Li, 3 ' 2 Ph Li, 3 aney i Al(g), etc Ph oreykim DM, l 2 DM, l ex.3 Et Et 3 i Pd Application U7,8 2. Ar Ar heat (syn elimination) Ar 1. base Ar oxid. 2. ArAr heat 4. Pummere eaction Ac 2 ' ' ( 3 ) 2 ' Ac ' Ac ' 3. Ar Evans earrangement 2 dipoledipole repulsion (Allyl sulfoxide) 87% yield Ph 3 Ph X (F 3 ) 2 Ph Ph 3 Ph Ph Ph Ph Ar Ar () 3 P

4 Biosynthesis of Penicillins 3 Enzyme 2 2 Arnstein tripeptide 2 Fe Fe 2 Fe 2 5. Dimethylsulfonium methylide 2 2 Dimethyloxosulfonium methylide 2 2 isopenicillin Biomimetic ynthesis of Penicillin Deriv. i t 2 Bu () Ph Ph i 2 Bu t Ph ZnI Ph 2 cis (~111) 2 PPh 3 PPh 3 lefine 6. eebach, orey Umpolung X nbuli Li a b a ' b D1. hiral ulfoxide () () FAM 2 MTsulfone

5 D2. Preparation of chiral sulfoxide (Andersen ) MgX 2 lmenthyl ()()ptolylsulfinate 2 P () () 2 P 2 1 'AlX 2 ZnBr 2 'AlX 2 a b Zn ' AlX 2 ' AlX 2 a b ' (1) ' (2) (1) (2) tbu 2 ZnBr 2 tbu 2 (n 7 15 ) 3 Al n 7 15 tbu 2 D4. Asymmetric cycloaddition DielsAlder reaction (hiral Auxiliary) n 9 19 n 9 19 MgX ZnBr 2 MgX t 97% ee >98% ee Dienophile ( 2 )n Diene ( 2 )n eactivity tereoselectivity Enantioselectivity

6 2 Et 2 Et Diene Et 2 Et endo exo 2 Et Ln eactivity as dienophile t Ln 2Pyridyl group EWG strong inductive electronwithdrawing group 2 n 1. s 4 2. acetone PPT TB 3. LiAl( t Bu) 3 4. TBl 1. Py, cat. Et 3 2. mpba 3. recrystalization 2 n 2 Py 2 n () DBU 2 n 1. D, DM 2. 2 =PPh 3 3. aq. F 3 2 n Dhowdomycin Py 2 n 1. s 4 2. acetone PPT 1. cat. Et 3 2 n 2. mpba F 3 3. recrystalization 2 n Ar Ar F 3 1. Til 3 2. LiAl 4 aq. F n () 0 Ar (982) 1. ()Glyoxalase I Inhibitor Ar 2. mpba 2 n 2, py

7 Asymmetric eduction of Ketones with AD Model ompounds arrying a hiral ulfoxide Functin Proton Pump Inhibitor PPI) (=,K ATPase ) prazole benzimidazole Pr 2 P P Ph X= (AD) X=P 2 2 (ADP) X 2 Mg 2 (AD, ADP) Ph ' methyl ()()mandelate 97% ee Ph si F 2 2 F 3 AstraZeneca AstraZeneca (1988, EU 1991, JP) (2000.8, EU 2001, U, , JP) WyethAyerst ( 2 ) 3 (2000.2, U) (1991, EU , JP 1995,U) ( , U 1997, JP) ynthesis of meprazole PPI * Enzyme Enzyme ) 3, 3 3 Ac , ) 3 1) a, Et(=) K mpba, 2 l 2 p 8.6, 5, 10 min ) l 2 l a, 2 Et reflux, 2 h 3 3 3

8 PAB (Pottasiumcompetitive acid blockers) = omeprazole (racemate) = 2 l PL F 3 ( ) harpless Asymmetric xid. Ti(iPr) 4, (,)DET ipr 2 Et, Ph() 2 > 94 % ee. ottn et al.(astrazeneca), TetrahedronAsymmetry, 11, 3819 (2000) a/ibu(mibk) rystal. from MIBK esomeprazole a a salt > 99.5 % ee,k ATPase