The stereospecific synthesis of all four stereoisomers of 2-amino-6-phenoxy-cyclohexanol,

Epoxidation of 3-phenoxycyclohexene 5 with m-chloro-perbenzoic acid gave 6 and 7 in a ratio of 9:1. These two epoxides were heated with a series of amines to give the aminophenoxycyclohexanol derivatives 1 and 2 respectively; in all cases the reaction was regio- and stereospecific. Two methods based on the principle of neighbouring group participation were developed to synthesize the cis-amino alcohols 3 and 4 . In the first, the hydroxy group was used to introduce an amine function at the vicinal carbon atom. In the second method, the amino group served as the point of reference and the configuration of the adjacent alcohol function was inverted.     

Conformationally constrained amino acids: enantiodivergent synthesis of all four stereoisomers of 2-(tetrahydrofuran-2-yl)glycine

The first enantiodivergent synthesis of all four possible 2-(tetrahydrofuran-2-yl)glycine stereoisomers is described. The key step of the route is the highly stereocontrolled allylboration of the (S)- or (R)-Garner's aldehydes to give four chiral homoallylalcohols. Starting from them, the title compounds are obtained in five steps.     

Synthesis of 2-oxazolidinones from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol

A series of isomeric 2-oxazolidinones has been synthesized from (1S, 2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 579–584, April, 2006.     

Enantio and diastereoselective total synthesis of all four stereoisomers of germicidin N

Abstract

Germicidin N (3-ethyl-4-hydroxy-6-[(1S, 2?R)?2-hydroxy-1-methylpropyl]-2H-pyran-2-one, 1), a new α-pyrone from the extracts of a Streptomyces sp. derived from marine algae, has been synthesized for the first time as four possible diastereomers from chiral β-hydroxyester ((S)?6 and (R)?9) through the stereoselective alkylation, Claisen condensation followed by cyclization in a straightforward manner.     

Concise total synthesis and stereochemical revision of all (-)-trigonoliimines

The concise and enantioselective total syntheses of (-)-trigonoliimines A, B, and C are described. Our unified strategy to all three natural products is based on asymmetric oxidation and reorganization of a single bistryptamine, a sequence of transformations with possible biogenetic relevance. We revise the absolute stereochemistry of (-)-trigonoliimines A, B, and C.     

An efficient stereospecific total synthesis of (±) terrein

Flash vacuum pyrolysis of functionalized tricyclo|5.2.1.0^2,3|decenone epoxide $\text{5}$, and acetals $\text{3}$ and $\text{4}$ affords cyclopentadienone epoxide $\text{6}$ and acetals $\text{10}$ and $\text{8}$, respectively. These epoxides are suitable precursors for the synthesis of (±) terrein.     

Synthesis of all of the possible stereoisomers of 4-benzamido-3-hydroxy-2-(δ-carbomethoxybutyl)thiophan

The stereospecific synthesis of the four possible isomers of 4-benzamido-3-hydroxy-2-(-carbomethoxybutyl)thiophan (III–VI) was accomplished from 4-benzamido-3-oxo-2-(-carbomethoxybutylidene)thiophan (I) using the stereospecificity of the reduction of the oxo group of I, the stereospecificity of the reduction of the exocyclic double bond of 4-benzamido-3-hydroxy-2-(-carbomethoxybutylidene)thiophan (II), and inversion of the hydroxyl group of III and IV. The configurations of the stereoisomers obtained were established by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 897–901, July, 1972.     

First total synthesis of (-)-ichthyothereol and its acetate

The first and stereoselective total syntheses of (-)-ichthyothereol (1) and its acetate ((+)-2) were achieved by incorporation of the two chiral centers of diethyl L-tartrate. The starting diethyl L-tartrate was converted into trans-2-ethynyl-3-hydroxytetrahydropyran 14 in a stereoselective manner via the endo mode cyclization of the epoxy-alkyne derivative 12. The alcohol 12 was then transformed into (E)-iodoolefin derivative 15, which was exposed to a coupling reaction with 1-tributylstannyl-1,3,5-heptyne (19), derived from the corresponding 1-trimethylsilyl-1,3,5-heptyne (18), under Stille conditions to produce the all-carbon framework of the target natural products. Chemical modification of the coupled product 20 under conventional conditions completed the first total synthesis of (-)-ichthyothereol (1) and its acetate ((+)-2).     

Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers

Total syntheses of (−)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi-dictyostatin, and a number of other isomers and analogs are reported. Three main fragments—top, middle, and bottom—were first assembled and then joined by olefination or anionic addition reactions. After appending the two dienes at either end of the molecule, macrolactonization and deprotection completed the syntheses. The work proves both the relative and absolute configurations of (−)-dictyostatin. The compounds were evaluated by cell-based measurements of increased microtubule mass and antiproliferative activity, and in vitro tubulin polymerization assays as well as competitive assays with paclitaxel for its binding site on microtubules. These assays showed dictyostatin to be the most potent of the agents and further showed that the structural alterations caused from 20- to >1000-fold decreases in activity.     

First total synthesis of (-)-AL-2

Treatment of the 3,4-dioxygenated-9-hydroxy-1-nonyn-5-one derivative, derived from diethyl l-tartrate, with a palladium catalyst in methanol under a CO atmosphere effected an intramolecular acetalization and a stereoselective construction of the (E)-methoxycarbonylmethylidene functionality resulting in formation of the core framework of the diacetylenic spiroacetal enol ether natural products. Chemical transformations of the 1,6-dioxaspiro[4.5]decane derivative thus formed led to the first total synthesis of (-)-AL-2. [reaction: see text]     

Fluorous mixture synthesis of (-)-dictyostatin and three stereoisomers

[reaction: see text] A mixture of four stereoisomers whose configurations are encoded by fluorous silyl protecting groups has been prepared and converted over 22 steps to a mixture of protected dictyostatins. Demixing by fluorous HPLC followed by removal of the fluorous protecting groups (detagging) provides dictyostatin and three C6,C7 stereoisomers. Biological evaluation showed that the monoepimers of the natural product retained highly potent activity.     

A short and stereospecific synthesis of (±)-α-lycorane

(±)-α-Lycorane (4) has been synthesized stereospecifically in five steps from commercially available 3,4-(methylenedioxy)phenylacetonitrile (7). The key step involves an intramolecular unstabilized iminium ylide-olefin [3+2] cyclo addition reaction 6 → 9.     

Regio-specific total synthesis of (±)-2-hydroxyaklavinone

The tricyclic quinone 8 was successfully synthesized from naphthazalin, and the total synthesis of (±)-2-hydroxyaklavinone via 8 was accomplished in an overall yield of about 18% through the regio-controlled route.     

Enantioselective total synthesis of (+)- and (-)-nigellamine A2

The nigellamine alkaloids are dolabellane diterpenes displaying potent lipid metabolism-promoting activity. Total synthesis of (+)- and (-)-nigellamine A2 has been accomplished. Absolute stereochemistry of synthetic nigellamine A2 was established through an intramolecular asymmetric allylic alkylation using a Pd(phosphinooxazoline) catalyst. Other notable transformations include a radical alkynylation, a diastereoselective Nozaki-Hiyama-Kishi cyclization, and a regio- and stereoselective catalytic epoxidation. On the basis of X-ray crystallographic analysis of an optically active intermediate, we have confirmed the assigned absolute stereochemistry of the natural product. Minor modifications of the synthetic sequence outlined here should provide access to the other nigellamine alkaloids.     

Synthesis and characterization of all stereoisomers of 8-phenylmenthol

New, improved and/or specific syntheses of the diastereoisomers of (−)-8-phenylmenthol are described. The configurations of these products, usable as chiral auxiliaries, were confirmed by X-ray diffractometry of their 3,5-dinitrobenzoates.     

Synthesis and sensory evaluation of all stereoisomers of sedanolide

Synthesis and sensory evaluation of all stereoisomers of sedanolide (1) are described. The asymmetric synthesis was achieved with using the all stereoisomers of bromoalcohol (3) prepared by enzymatic resolution and inversion of the secondary alcohol. All four stereoisomers of 1 were obtained in high enantiomeric purities (>99% ee). Their sensory evaluation revealed that there were distinct differences among the stereoisomers.     

Regioselective and diastereoselective amination with use of chlorosulfonyl isocyanate: a short and efficient synthesis of (-)-cytoxazone

The total synthesis of (-)-cytoxazone 1 was achieved in six linear steps (34% overall yield) from p-anisaldehyde. The key steps in this route are the regioselective and stereoselective introduction of a N-protected amine group, using the CSI reaction of the anti-1,2-dimethyl ether 3, and the subsequent regioselective cyclization of the N-protected amino diol 13 to give the 2-oxazolidinone unit of (-)-cytoxazone 1. [reaction: see text]