Synthesis of enantiopure (R,R)- and (S,S)-cis-2,3-propanoprolines

A novel approach to the synthesis of an enantiopure bicyclic proline analogue, hexahydrocyclopenta[b]pyrrole-6a(1H)-carboxylic acid (‘2,3-propanoproline’), has been developed. The method relied on tandem Strecker-nucleophilic cyclization reaction of 2-(2-bromoethyl)cyclopentanone. The overall synthetic scheme included six steps and resulted in 18% overall yield of both enantiomers of the title amino acid.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

(R,R)-2,3-Butanediol and (s)-pinanediol allylboronates in chiral synthesis of (2S,3S)-3-methyl-5-hexen-2-ol

(R,R)-Butanediol (dichloromethyl)boronate ( 1 ) with 1 equiv. allylmagnesium halide yields (R,R)-2,3-butanediol (1S)-(1-chloro-3-butenyl)boronate ( 3 ) together with the diallylated product (R,R)-2,3-butanediol (1-allyl-3-butenyl)boronate ( 4 ). The formation of 4 is unprecedented in reactions of α-chloroboronic esters with Grignard reagents. With methylmagnesium bromide 3 yielded (R,R)-2,3-butanediol (1S)-(1-methyl-3-butenyl)boronate ( 5 ), which failed to hydrolyze with water. Hydrolysis of 3 yielded impure α-chloroboronic acid, which was esterified with pinacol and treated with methylmagnesium bromide to form 6 , which with (dichloromethyl)lithium followed by methylmagnesium bromide yielded diastereomeric boronic esters 7 and 8 . Oxidation by hydrogen peroxide yielded (2S,3S)- and (2R,3S)-3-methyl-5-hexen-2-ol ( 9 and 10 , ees unknown). Treatment of (s)-pinanediol allylboronate ( 11 ) with (dichloromethyl)lithium at −100°C followed by zinc chloride at up to 25°C has proceeded in the normal way to form (s)-pinanediol (1S)-(1-chloro-3-butenyl)-boronate ( 12 ), which has been elaborated via 13 , 14 , and 15 to (2S,3S)-3-methyl-5-hexen-2-ol ( 9 ) in 95% de.     

Preparation of Enantiomerically Enriched (2R,3R)- or (2S,3S)-trans-2,3-Diaryloxiranes via Camphor-Derived Sulfonium Ylides

Easily available D-(+)-camphor-derived sulfides 3, 4, 6, and 7 were employed for enantioselective epoxidation via an ylide route. When benzylated or methylated sulfides were used as reagents or mediators for benzylidene transfer, stoichiometric and catalytic epoxidations were realized, respectively. Opposite asymmetric induction was achieved only when sulfides containing exo- (3 and 4) and endo- (6 and 7) alkylthio groups were used. That is, both (+)- and (-)-trans-diaryloxiranes could be obtained in excellent yields and moderate to good ee values under extremely mild conditions from the same chiral pool-derived reagents. A nonbonded interaction between the free OH in the ylides from sulfides (3, 6, and 7) and the carbonyl group of aldehydes controls the approach of the substrates to the ylidic carbon preferentially at one specified face and therefore leads to a more efficient asymmetric induction than that in the case of the ylide from methyl-protected hydroxylated sulfides 4, which cannot cause such an interaction. The same opposite asymmetric induction was also observed in the catalytic reaction with methyl-protected hydroxylated sulfide 4b and unprotected hydroxylated sulfide 3b.     

从D-甘露糖醇制备(R)和(S)-3,3-二甲基-2,3-O-异亚丙基甘油酸甲酯

本文提出了一种由D-甘露糖醇出发合成一对高光学纯度的异亚丙基保护的3,3-二甲基甘油酸甲酯2a和2b的有效方法     

Asymmetric total synthesis of 14(R),15(S)-, 14(S),15(R)-, 14(R),15(R)-, and 14(S),15(S)-epoxyeicosatrienoic acids

The four chiral stereoisomers of 14,15-oxido-5Z, 8Z, 11Z-eicosatrienoic acid were synthesized. The absolute stereochemistry in each case was derived from an asymmetric epoxidation of E-2-octen-1-ol.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

Chemoenzymatic preparation of (2S,3S)- and (2R,3R)-2,3-butanediols and their esters from mixtures of d,l- and meso-diols

An efficient method of preparing the pure enantiomers of 2,3-butanediol from commercially available mixtures of the d,l- and meso-isomers was developed. It furnished (2S,3S)-2,3-butanediol with >99% e.e. and a >99.5/0.5 diastereomeric ratio and (2R,3R)-2,3-butanediol in 95% e.e. and >95/<5 diastereomeric ratio.     

Asymmetric synthesis of (S,R)- and (R,R)-methiin stereoisomers

Abstract

An asymmetric synthesis of (+)- and (–)-methiine (S-methyl-(R)-cysteine sulfoxide) diastereomers has been developed. These natural sulfur compounds were isolated from a variety of Brassica vegetables. As the starting compound, (R)-cysteine was used, which was methylated to form (R)-S-methylcysteine. Then the oxidation of S-methylcysteine with tert-butyl hydroperoxide catalyzed by the chiral tetra(isopropylate)titanium/(S)- or (R)-Binol complex led to the formation of (1?R,2S)-(+)- or (1?R,2R)-(–)-methiin stereomers.     

Synthesis of (S,R,R,S,R,S)-4,6,8,10,16,18- hexamethyldocosane from Antitrogus parvulus via diastereoselective hydrogenations

[structure: see text]. The hydrocarbon 1 was prepared via a series of catalyst-controlled diastereoselective hydrogenations beginning with fragments derived from the Roche ester.     

Synthesis of (5R,8S,10R)-6-(Allyloxy)- and (5R,8S,10R)-6-(Propyloxy)ergolines from the 6-Methyl Precursors

Novel (5R,8S,10R)-6-(allyloxy)- and (5R,8S,10R)-6-(propyloxy)ergolines have been synthesized by use of a Meisenheimer [2,3]-sigmatropic rearrangement of a (5R,8S,10R)-6-allyl-ergoline N⁶-oxide as key step.     

Asymmetric Synthesis of (-)-(2R,3R,6S)-Irnigaine

Introduction　　Asarelativelynewmemberofnaturalalkaloidswith2 ,6 disubstituted 3 piperidinolskeleton ,irnigaine 1wasisolatedfromthetubersofArisarumVulgare (Araceae)in1995byMelhaouiandBode .1Itsstructureandrelativeconfigurationswereelucidatedby1HNMRstudiesandtheabsoluteconfigurationwasproposedonthebasisofitsopti calrotation .1Soonafterthen ,Meyerandhisco workersreportedthefirstsynthesisof (- ) (2R ,3R ,6S) irni gaineandtheconfigurationconfirmation .Althoughtheirsynthesisroutewasshortan…     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Total synthesis of (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A and (-)-(6S,7S,8S,9R,10S)- membrenone-B and structural assignment of membrenone-C

[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.     

Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid

(2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid 1b have been synthesised for use in biosynthetic and metabolic studies.