Asymmetric synthesis of (−)- and (+)-neodichroine/hydrachine A from (+)- and (−)-febrifugine

A new asymmetric approach to both enantiomers of the quinazolinone-containing natural product febrifugine is reported. Utilising a proline-mediated aminooxylation-Horner-Wadsworth-Emmons sequence provides the key optically active 2,3-disubstituted piperidine intermediate 7 in high enantioselectivity but poor overall yield (7 steps, 3%, 98% ee). This intermediate has been used to prepare both naturally occurring (+)-febrifugine (1) and its (?)-enantiomer. In turn, each were then used to synthesise, for the first time, both enantiomers of the claimed natural product neodichroine/hydrachine A. Spectroscopic data for the synthetic compound matched the claimed structure. However, the specific rotation differed in both magnitude and sign from the isolation work.     

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.     

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.     

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.     

Optimization of <Emphasis Type="Italic">α</Emphasis>-Terpineol Production by the Biotransformation of <Emphasis Type="Italic">R</Emphasis>-(+)-Limonene and (−)-β-Pinene

The main objective of this work is to present the optimization of the biotransformation of R-(+)-limonene and (−)-β-pinene aiming at the production of α-terpineol by strains of fungal and yeasts previously isolated by our research group using the methodology of experimental design. New optimized experimental data on α-terpineol production by the biotransformation of R-(+)-limonene and (−)-β-pinene using newly isolated microorganisms are reported in this work. Conversion of about 1,700 mg/L was achieved when R-(+)-limonene was used as substrate and the newly isolated strain 05.01.35 as microorganism at the central point of the experimental design, corresponding to a substrate concentration of 1.75%, mass of inoculum of 2 g, and substrate to ethanol volume ratio of 1:1. The same experimental condition led to higher conversions when (−)-β-pinene was used as substrates and the strains coded as 04.05.08 and 01.04.03 as microorganism. Here, conversions of about 770 mg/L were achieved.     

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.     

Concise enantiodivergent synthesis of (+)- and (−)-trans-quercus lactones

A concise enantiodivergent total synthesis of (+)- and (−)-quercus lactones from the known tricyclic lactone (+)-1 as a single chiral template was achieved using the diastereoselective nucleophilic addition of organometallic reagents as the key step.     

Total synthesis of natural (−)- and unnatural (+)-Melearoride A

This communication details the first total synthesis of the 13-membered macrolide, (?)-Melearoride A, as well as unnatural (+)-Melearoride A. The synthesis features a concise 13 step synthesis (11 steps longest linear sequence) that offers flexible stereo-control and multiple opportunities for unnatural analog synthesis to delve into antifungal SAR. The route features a cuprate addition, an Evans asymmetric alkylation, and a ring-closing metathesis (RCM) to close the 13-membered macrocyclic core.     

Alkylation of 2,4-dimethylphenol with (+)-α- and (−)-β-pinenes in the presence of aluminum xylenolate

Alkylation of 2,4-dimethylphenol with (+)-α- and (?)-β-pinenes in the presence of aluminum 2,4-dimethylphenoxide generated in situ led to the formation of mixtures of products, from which optically active compounds were isolated. The structure of 2-bornyl-4,6-dimethylphenol was determined by X-ray analysis; its (+)- and (?)-enantiomers were assigned (1R,2R,4S) and (1S,2S,4R) configurations, respectively.     

Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine

Abstract

Tetrabenazine (1) was reduced with NaBH₄ to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (?)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (?)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.     

A simple asymmetric synthesis of (+)- and (−)-2,6-diaminopimelic acids

The asymmetric synthesis of both the enantiomers of 2,6-diaminopimelic acid (2,6-DAP) has been accomplished starting from the chiral synthon 1.     

Total syntheses of macrosphelides (+)-A, (−)-A and (+)-E

Total syntheses of (+)-macrosphelide A 1 (18.5% overall yield in 11 steps) and (+)-macrosphelide E 2 (23.9% overall yield in 11 steps) have been achieved via the chemoenzymatic reaction product (4R,5S)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4. The enantiomer (−)-A (1) (14.2% overall yield in 11 steps) of (+)-1 was also synthesized from the chemoenzymatic reaction product (4S,5R)-4-benzyloxy-5-hydroxy-2(E)-hexenoate 4.     

Large scale preparation of (+)- and (−)-endo-norbornenol by enzymatic hydrolysis

A multigram preparation of (+)-(1R,2R,4R)-endo-bicyclo[2.2.1]hept-5-en-2-ol ((+)-2) and its enantlomer (−)−2 with an optical purity of 90% and > 96%, respectively, was accomplished via enantioselective hydrolysis of (±)-5-endo-norbornen-2-ylacetate using lipase from Candida cylindracea.     

First synthesis of (+)- and (−)-elvirol based on an enzymatic function

A highly enantioselective synthesis of versatile chiral synthons possessing one stereogenic center, (S)- and (R)-4-aryl-5-hydroxy-(2E)-pentenoate 3 was achieved based on the enzymatic reaction of (±)-4 with commercially available lipase ‘OF-360’ from Candida rugosa. An application of (S)-3 and (R)-3 to the total syntheses of (S)-elvirol 1 and (R)-elvirol 1, respectively, is described.     

Stereoselective total synthesis of (−)-zeylenol,a key intermediate for the synthesis of (+)-pipoxide, (−)-uvarigranol G and (−)-tonkinenin A

Total synthesis of (?)-zeylenol, a key intermediate for the synthesis of (+)-pipoxide, (?)-uvarigranol G and (?)-tonkinenin A was achieved from commercially available starting material d-mannose. The key steps are mixed aldol condensation, Grignard reaction, ring closing metathesis and regioselective benzoylation.     

Efficient synthesis of (−)-(R)- and (+)-(S)-rolipram

A novel, efficient and protecting group free enantioselective synthetic approach of (?)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization reactions as key steps.     

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.     

Asymmetric total synthesis of (+)-isocryptotanshinone and formal synthesis of (−)-cryptotanshinone

The first asymmetric total synthesis of (+)-isocryptotanshinone was achieved in 12 linear steps with 12% overall yield from commercially available dihydrobenzopyrone. The key step was a base-mediated cyclization reaction. In addition, the synthetic strategy included the formal synthesis of (−)-cryptotanshinone.