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A regio- and stereoselective intramolecular direct aldol reaction of 2,7-diketones derived from carbohydrates has been developed to construct cycloalkanones 7, which were dehydrated to obtain heavily oxygenated cycloalkenones 8.

A new class of human GST inhibitors has been identified via rational design approach; we report their discovery, synthesis, inhibitory activity, and synergetic effect in combination with cisplatin against A549 lung cancer cell line. The results of this effort show that the lead 4-O-decyl-gabosine D (24) has optimum synergetic effect in A549 human lung adenocarcinoma epithelial cell and that this activity involves inhibition of glutathione S-transferase M1, apparently consistent with siRNA-mediated knockdown of GSTM1 gene.

Gabosine K, whose structure was erroneously assigned previously as 7-O-acetyl-4-epi-streptol, has been synthesized for the first time from D-glucose via a key carbocyclization strategy, intramolecular direct aldol reaction of a 2,6-diketone, in 15 steps with 13.5% overall yield. In the same manner, (+)-7-O-acetyl-streptol has been constructed for NMR spectral comparison. The structure, relative and absolute configurations of (―)-gabosine K are now revised and established as (―)-7-O-acetyl-1-epi-streptol, that is, (1R,2S,3S,4R)-tetrahydroxy-5-acetoxymethylcyclohex-5-ene. Since the specific rotation of the natural product is not available, the absolute configuration of natural gabosine K is either (―)-7-O-acetyl-1-epi-streptol or its enantiomer.

An alternative synthesis of 1,1'-bis-valienamine 5, which was demonstrated to be a potent trehalase inhibitor, has been achieved from d-glucose in 12 steps with 15% overall yield via enone 12 as the key intermediate, involving a direct aldol reaction of a glucose-derived diketone and a palladium-catalyzed allylic coupling reaction as the key steps.

A new and stereoselective intramolecular direct aldol reaction of diketones derived from carbohydrates has been developed to construct carbocycles with d-gluco-, d-galacto-, d-manno-, and l-ido-configurations. The stereochemical outcome of the aldol reaction of the diketone is dependent on the base used. Transformation of d-gluco-aldols readily affords valiolamine which also constitutes a formal synthesis of voglibose. Facile conversion of d-gluco-cyclohexanones into validoxylamine G has been achieved in 12 steps with 15.1% overall yield from d-glucose.

A pseudo-1,4'- N-linked disaccharide, pseudoacarviosin 5, was constructed via a key palladium-catalyzed coupling reaction of pseudoglycosyl chloride 8 (prepared from d-glucose via a novel direct intramolecular aldol addition in 12 steps) and pseudo-4-amino-4,6-dideoxy-alpha- d-glucose 9 (prepared from l-arabinose via an unusual trans-fused isoxazolidine-selective intramolecular nitrone-alkene cycloaddition in 11 steps). Pseudoacarviosin 5 has been shown to be a potent inhibitor of alpha-glucosidases, particularly the intestinal mucosal enzymes sucrase and glucoamylase of relevance to blood glucose control.

A short synthesis of gabosine I (1) from δ-d-gluconolactone (3) in four steps, involving a one-pot TPAP oxidation−K2CO3-mediated intramolecular Horner−Wadsworth−Emmons (HWE) olefination as the key step, is described. Regioselective acetylation of the primary alcohol in gabosine I (1) then furnished gabosine G (2).

A short synthesis of gabosine I (1) from delta-D-gluconolactone (3) in four steps, involving a one-pot TPAP oxidation-K2CO3-mediated intramolecular Horner-Wadsworth-Emmons (HWE) olefination as the key step, is described. Regioselective acetylation of the primary alcohol in gabosine I (1) then furnished gabosine G (2).

[reaction: see text] Intramolecular nitrile oxide-alkene cycloaddition (INOC) of sugar derivatives with one to four free hydroxyl group(s) is reported. The INOC reaction, using chloramine-T, in the presence of silica gel, to generate nitrile oxides from oximes, proceeded smoothly to afford five- or six-membered carbocycles in good to excellent yields. This new methodology alleviates protection/deprotection steps and makes the synthetic route shorter and more efficient.

(+)-Gabosines A (12), D (4), and E (5), which share the same trihydroxycyclohexenone skeleton, were synthesized from enone 11 as the common intermediate. The key building block 11 was accessed by an intramolecular aldol cyclization of a diketone derived from D-glucose (8).