Stereoselective synthesis of polyhydroxylated aminocyclohexanes

The stereoselective synthesis of a series of di- and tri-hydroxylated aminocyclohexane derivatives has been developed. A one-pot, two step tandem process involving an Overman rearrangement and a ring closing metathesis reaction has been utilised for the asymmetric synthesis of (1S)-1-(2',2',2'-trichloromethylcarbonylamino)cyclohexa-2-ene. Oxidation of this cyclohexene derivative was then studied leading to the preparation of two diol analogues in excellent stereoselectivity. (1S)-1-(2',2',2'-trichloromethylcarbonylamino)cyclohexa-2-ene was then converted to a novel allylic alcohol via a 4,5-dihydro-1,3-oxazole. Functionalisation of this allylic alcohol by Upjohn dihydroxylation conditions or by a directed epoxidation/hydrolysis sequence of reactions allowed the synthesis of two dihydroconduramines in excellent stereoselectivity. The stereochemical assignment of all compounds prepared was confirmed by NOE experiments or X-ray structure determination.     

Stereoselective synthesis of polyhydroxylated quinolizidines from C-glycosides by one-pot double-conjugate addition

An effective one-pot synthesis of polyhydroxylated quinolizidines from 1-C-(2'-oxo-4'-pentenyl)-5-azido-C-glycofuranosides was developed. Reduction of the 5-azido group using triphenylphosphine followed by base treatment produced quinolizidines in good yield. The base-mediated ring-opening beta-elimination produced an acyclic alpha,beta-conjugated ketone as a Michael acceptor, which was followed by an intramolecular nitrogen conjugate addition to form an aza-C-glycopyranoside intermediate. Meanwhile, the beta,gamma-double bond of the aglycon migrated under the basic conditions to form another alpha,beta-conjugated ketone. The subsequent intramolecular conjugate addition by the azasugar nitrogen led to the formation of the quinolizidines in a highly stereoselective manner. The stereoselectivity of the first conjugate addition giving azasugar is affected by the stereochemistry of the monosaccharide substrate, whereas the stereoselectivity in the second conjugate addition was likely directed entirely by steric repulsion from the azasugar.     

Iminosugars from α,β-epoxyamides. Part 2: Synthetic approach to hydroxylated pyrrolidine and azepane derivatives

This paper describes a new synthetic route towards hydroxylated pyrrolidines and azepane derivatives starting from chiral epoxyamides. The alternate transformations on a ribose derivative α,β-epoxyamide permit the construction of five or seven member rings leading to different precursors of homoiminosugars.     

Stereoselective synthesis of pseudotripeptides incorporating uncommon bis-α-aminoacid derivatives and X-ray analysis. Part 3

Stereoselective synthesis of pseudotripeptides 4, 5, 6, 8, 9, 13 and 14, incorporating an uncommon bis(α-aminoacid) derivative, has been accomplished starting from the L-valine derived chiral synthon 1. The configuration of the introduced stereogenic centres has been assigned on the basis of ¹H NMR spectroscopic data. The geometry of the tripeptides, deduced on the basis of ¹H NMR parameters and IR spectra, was confirmed by X-ray crystal structure analysis of 6.     

Enantiospecific synthesis of polyhydroxylated indolizidines related to castanospermine:1 1-deoxy-castanospermine.

Enantiospecific synthesis of (6S,7R,8R,8aR)-6,7,8- trihydroxyindolizidine ( 1-deoxy-castanospermine ) (3) is described from readily available D-glucose, where the key step involves oxidative bromination of a benzylidene acetal to afford 8-azido-3-o-benzoyl-5-bromo-5,6,7,8-tetradeoxy-1,2-o-isopropylidene-β-L-ido-octose (16). The synthetic indolizidine (3) was tested against a range of glycosidases.     

Stereoselective synthesis of sterically constrained dipeptides. Part 2

The alkylation of the diastereomeric mixture of lactims 2 and 3 occurs in total regioselectivity and good to high facial stereoselectivity (d.s. ranging from 82 to 97%). Cleavage of the lactim 4e gives enantiomerically pure dipeptide 12, sterically constrained at the α-carbon. The absolute configuration of the new stereocentres has been assigned on the basis of ¹H-NMR data and NOE measurements.     

Stereoselective synthesis of bis-steroidal pyrazine derivatives

Some compounds of Cephalostatin family have shown anti-cancer activity against human cancer cell line and active intensity has close with the stereochemistry of the substituted group, for example, beta-OH at C-12 in compound 2 showed less promising results and the mixture 3 (alpha + beta) showed a large enhancement of the activity compared to the compound 2. So, the work was concentrated on the synthesis diastereomers 10 and 11 were obtained in a pure form.     

Stereoselective syntheses of 20-epi cholanic acid derivatives from 16-dehydropregnenolone acetate

A stereoselective total synthesis of naturally occurring 20-epi cholanic acid derivatives has been realized, starting from readily available 16-dehydropregnenolone acetate. The key step of these syntheses involves an ionic hydrogenation of a C-20,22-ketene dithioacetal and deoxygenation of steroidal C-20 tert-alcohols, to set up the unnatural C(20R) configuration with 100% stereoselectivity. The unnatural C-22 aldehydes with C(20R) stereocenters thus obtained were elaborated to 20-epi cholanic acid derivatives. Two derivatives of 20-epi cholanic acid were synthesized and their structures have been confirmed by single crystal X-ray analysis. Catalytic hydrogenation of 16-dehydropregnenolone acetate and 16-dehydropregnenolone in ethanol affords C-5,C-16 tetrahydro products. Crystal structure analysis of one of these products revealed C-5α and C-17α configurations of the hydrogen atoms.     

Stereoselective strategy for the synthesis of (+)-polyoxamic acid and some polyhydroxylated pyrrolidines

An efficient strategy for the synthesis of dihydroxy chiral amino moiety which can be utilized for the synthesis of polyoxamic acid, 1,4-dideoxy-1,4-imino-d-xylitol, and dihydroxy pyrrolidine by using highly diastereoselective nucleophilic addition on chiral imine has been reported.     

Diastereoselective synthesis of 1-benzyltetrahydroisoquinoline derivatives from amino acids via 1,4 chirality transfer. Part 1

[structure: see text]. L-(-)-phenylalanine, L-(+)-valine, and L-(-)-proline were used in the diastereoselective synthesis of benzyltetrahydroisoquinoline derivatives.     

Studies on the syntheses of heterocyclic compounds. Part DCXII. A simple synthesis of benzopyran and dibenzopyran derivatives

trans-2-(3-Hydroxyphenyl)cyclohexanol (1b) was converted into 6-methyl-6-phenylbenzopyran (11a) and 6-spirocyclohexanobenzopyran (11b) by phenolic cyclization or under acidic condition. This type of reaction was also applied to the synthesis of 3,4-dihydro-6-methoxy-1-methoxycarbonyl-1-methyl-1H-2-benzopyran (IV).     

Stereoselective synthesis of partially protected azasugar derivatives

Five-membered azasugar derivatives with partially protected hydroxyl groups, and their fluorinated derivatives were synthesized via the key intermediates of norbornyl-like bicyclic acetals using d-xylose and d-glucose as starting materials. The glycosylation of the azasugar intermediate and 1-methylenesugar was also explored. Translated from Chemical Journal of Chinese Universities, 2006, 27 (4) (in Chinese)     

Stereoselective synthesis of polyhydroxylated indolizidines based on pyridinium salt photochemistry and ring rearrangement metathesis

Ruthenium-catalyzed ring rearrangement metathesis (RRM) reactions of stereochemically diverse, differentially protected 4-N-allylacetamidocyclopenten-3,5-diols, prepared by using pyridinium salt photochemistry, have been explored as part of a program to develop novel routes for the synthesis of polyhydroxylated indolizidines. The RRM reactions, which produce selectively protected 1-acetyl-2-allyl-3-hydroxy-1,2,3,6-tetrahydropyridines, were found to take in high yields and with high levels of regioselectivity. The significance of RRM reactions of 4-N-allylacetamidocyclopenten-3,5-diols in the context of polyhydroxylated indolizidine synthesis is demonstrated by an application to the concise preparation of the potent glycosidase inhibitor, (-)-swainsonine.     

Stereoselective synthesis and conformational analysis of pseudo-heptapeptides: Part 5

The stereoselective synthesis of pseudo-heptapeptides 8, 9 and 12, incorporating a 2,6-diamino-4-methylen-1,7-heptanedioic acid residue, was accomplished starting from chiral synthon 3, a masked unnatural dipeptide derived from an l-valine unit and (2R)-methylaspartic acid. Investigations of the conformational preference and structure of these unnatural peptides were carried out using ¹H NMR and IR spectroscopic data and a conformational analysis based on molecular dynamics (MD).     

Stereoselective synthesis and conformational analysis of unnatural tetrapeptides. Part 2

Stereoselective synthesis of unnatural tetrapeptides 20a and 20b, 21a and 21b and 30 and 31, containing two l-valine units and two unnatural α-amino acids (ornithine and modified aspartic acid), has been accomplished starting from the l-valine derived chiral synthon 1. Structural investigations of these non-proteinogenic peptides have been carried out on the acetamido derivatives using ¹H NMR, IR spectroscopic techniques and a conformational analysis based on molecular dynamics (MD) and cluster analysis.