Stereospecific Synthesis of (−)-β-Turmerone and (−)-Bisacurol

The structure of (+)-β-turmerone ((+)- 1a ), a constituent of the rhizomes of Curcuma longa Linn. , and Curcuma xanthorriza, is established as (1′R,6S)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-one by synthesis of its enantiomer (−)- 1a , and of the corresponding (1′S,6S)-diastereoisomer (+)- 1b as well. In a stereospecific seventeen-step procedure, the monoterpene diols 2a and 2b of well-established configuration are converted into the target compounds (−)- 1a and (+)- 1b , respectively. Moreover, (−)-bisacurol (−)- 3a (II), the enantiomer of another bisabolane sesquiterpene derived from Curcuma xanthorriza, is obtained as a single stereoisomer and shown to be (1′S,6R)-2-methyl-6-(4′-methylenecyclohex-2′-en-1′-yl)hept-2-en-4-ol, the relative configuration at the remaining OH-substituted chiral center C(4) still being unknown.     

Expedient syntheses of indolizidines (−)-167B and (−)-209D

Indolizidine alkaloids (−)-167B and (−)-209D were synthesized via an expedient route using hydroacylation and amination.     

Synthesis of (S)-(−)-β-cuparenone and (S)-(−)-cuparene

A short and efficient synthesis of the title compounds is described. (S)-(−)-β-Cuparenone was prepared in 31% yield from p-tolualdehyde and mesityl oxide in eight steps. Absolute stereochemistry was established by means of a diastereoselective cyclopropanation using (R,R)-hydrobenzoin as a recoverable auxiliary.     

Enantioselective synthesis of (−)-γ-jasmolactone

The title compound was prepared in seven steps starting from the commercially available 4-ketopimelic acid. The key step features an enantioselective lactonization promoted by PPL.     

A simple synthesis of (−)-(R)-ipsdienol and (−)-(S)-ipsenol

A short and efficient synthesis of the unnatural enantiomer of (+)-(S)-ipsdienol 1 and (−)-(S)-ipsenol 2 is presented via an asymmetric allylboration. The synthesis was achieved by using a one-pot reduction–methylenation of an exo-methylene lactone intermediate.     

The configurations of (−)-2,3,3-trimethyl-2-hydroxybutanoic acid,Me3CC(Me)(OH)CO2H, (−)-3,3,4-trimethyl-3-hydroxy-1-pentyne and (−)-3-t-butyl-3-methyl-1-chloroallene

The configurations of the title compounds are reassigned, based on stereoselective syntheses of the hydroxyacid and corresponding glycol and application of Cram's, Prelog's and Sharpless' rules.     

Synthesis of R-(−)-2-phenylpropanal: a potentially new route towards chiral 2-phenylalkanals

A facile two step synthesis of (R)-2-phenylpropanal in high enantiomeric excess is described, starting from commercial (S)-styrene oxide, involving as a key step a Dess–Martin oxidation.     

An efficient synthesis of enantiopure (+)- and (−)-3-exo-amino-7,7-dimethoxynorbornan-2-exo-ols

We describe the synthesis of new amino alcohols (+)- and (−)-3-exo-amino-7,7-dimethoxynorbonan-2-exo-ols. The (+)- or (−)-7,7-dimethoxy-1,4,5,6-tetrachlorobicyclo[2.2.1]hept-5-en-2-endo-ol, obtained from the enzyme catalysed transesterification of the racemate, was reduced and dechlorinated (Na/NH₃; ethanol), followed by pyridinium chlorochromate oxidation of the resultant alcohols to the corresponding ketones. After treatment with t-BuOK/BuONO, in a nitrosation reaction, α-keto oximes were obtained. Reduction over two steps with NaBH₄ and NaBH₄/NiCl₂·6H₂O followed by in situ acetylation furnished the corresponding acetamido esters, which were hydrolysed with CH₃OH/Na to produce the enantiopure amino alcohols in good yields.     

Synthesis of (+)- and (−)-Phaselic Acid

The syntheses of both enantiomers of phaselic acid (2-O-caffeoylmalate) are described. The previously unreported acetate-protected caffeic acid anhydride was used with appropriately protected malic acid derivatives as coupling partners to provide fully protected phaselic acid. Sequential unmasking of the protecting groups afforded phaselic acid in an acceptable overall yield.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Enantioselective syntheses of (+)- and (−)-brazilin

Two enantiomers of brazilin were prepared in 9 steps from 7-hydroxychroman-4-one using the AD-mix-α and AD-mix-β-directed enantioselective dihydroxylation of 3-(4-hydroxy-3-methoxyphenyl)-2H-chromen-7-ol as a key step.     

Enantiodivergent synthesis of (+)- and (−)-isolaurepan

The enantiodivergent synthesis of (+)-and (?)-isolaurepan was achieved from a common chiral template easily available from tri-O-acetyl-d-glucal, using as key step a diastereoselective thermal Claisen rearrangement, combined with a ring expansion reaction using trimethylsilyldiazomethane.     

Total synthesis of (−) verbenalol and (−) epiverbenalol

The first asymmetric synthesis of (−) verbenalol and (−) epiverbenalol, starting from the organometallic complex (−) 1, is described.     

A concise synthesis of (S)-(−)-3-(2-carboxy-4-pyrrolyl)-alanine

A convergent synthesis of (S)-(−)-3-(2-carboxy-4-pyrrolyl)-alanine (CPA) 1, a non-proteinogenic amino acid is described starting from a commercially available dimethyl l-aspartate 2 in good overall yield.     

Diastereoselective α-iminoamine rearrangement: asymmetric synthesis of (R)-(−)- and (S)-(+)-2-benzyl-2-hydroxycyclohexanone

A convenient asymmetric synthesis of both (R)-(−)- and (S)-(+)-2-benzyl-2-hydroxycyclohexanones starting from racemic 2-benzyloxycyclohexanone and the chiral auxiliary 1-phenylethylamine is reported. The route involves a [1,3]-sigmatropic shift and a new diastereoselective α-iminoamine rearrangement of a 2-benzyl-2-iminocyclohexanamine substrate.     

Total Synthesis of (R)-(−)-β-Cuparenone

Abstract

(R)-(?)-β-Cuparenone has been synthesized from (S)-(+)-acid-2 obtained via resolution of the racemic acid. Two of the noteworthy steps are (a) repeated methylation of ester (+)-8 with LDA/MeI to furnish (+)-10 and (b) the reaction of 12, having two neopentyl units with NaCN.     

Stereoselective synthesis of (−)-6,7-dehydroferruginyl methyl ether

A stereoselective synthetic route to (−)-6,7-dehydroferruginyl methyl ether was developed from (S)-(−)-α-cyclocitral.     

Asymmetric synthesis of (−)-(R)-sitagliptin

The asymmetric synthesis of (?)-(R)-sitagliptin was achieved in seven steps from commercially available starting materials using the highly diastereoselective conjugate additions of either lithium (R)-N-benzyl-N-(α-methylbenzyl)amide or lithium (R)-N-benzyl-N-(α-methyl-p-methoxybenzyl)amide to tert-butyl 4-(2′,4′,5′-trifluorophenyl)but-2-enoate to install the correct stereochemistry. Subsequent sequential acid-catalysed hydrolysis of the resultant β-amino esters, HOBt/EDC mediated coupling with the triazolopyrazine fragment, and hydrogenolysis gave (?)-(R)-sitagliptin in 43% and 42% overall yields, respectively.     

The synthesis of (−)-cis- and (−)-trans-crobarbatic acid

The synthesis of both cis- and trans-crobarbatic acid is reported. The five-step sequence proceeds in high yield and with control of both relative and absolute stereochemistry. The key step in the synthesis is the Birch reductive alkylation of a chiral furoic acid which sets the absolute stereochemistry of the products. The stereochemistry of the compounds described was proven unambiguously by X-ray crystallography on one synthetic intermediate and on trans-crobarbatic acid.     

Scaleable processes for the synthesis of (−)-β-d-2,6-diaminopurine dioxolane (Amdoxovir,DAPD) and (−)-β-d-2-aminopurine dioxolane (APD)

An efficient and scalable synthesis of (?)-DAPD and (?)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved β-selectivity and an isolated yield four-fold greater than the original process scale method. Using this new process, (?)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (?)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water soluble deprotected α-anomer while leaving the β-anomer completely untouched.     

Biogenetically-modelled total syntheses (−)-nocardicin A and (−)-nocardicin G

A protected form of L-seryl-D-(p-hydroxyphenyl)glycine was cyclized in a biogenetic sense and partially deprotected to give (−)-t-butyl 3-amino nocardicinate (5) from which (−)-nocardicin A (1) and (−)-nocardicin G (11) were prepared.