Francisco Sarabia-García

Studies on the synthesis of tunicamycin. The preparation of 7-deoxy-2-deamino-6-hydroxy tunicamine and related products

Abstract The condensation of methyl 5-deoxy-5-diazo-2,3-O-isopropylidene-β-D-ribofuranoside with 1,2:3,4-di-O-isopropylidene-D-galactohexonodialdo-1,5-pyranoside gave the ketone C-disaccharide 11 as the sole product. This ketone was transformed into different derivatives. Thus, its reduction led stereoselectively to the corresponding alcohols. Similar transformations led to the corresponding alkane and amino derivatives, of potential biological interest as inhibitors for glycosidases. These results can be useful for the synthesis of tunicamine and its analogues.

Asymmetric synthesis of 2,3-epoxyamides by reacting monosaccharide derivatives with stabilised sulphur ylides generated in-situ: two-phase method and configurational assignations

Abstract The reaction of 2,3- O -isopropylidene-D-glyceraldehyde 1 ,2,4-ethylidene-D-threose 7 , or 2,3:4,5-di- O -isopropylidene-D-arabinose 9 with N,N-dimethyl-carbamoylmethyldimethylsulphonium chloride and a 10–50% solution of sodium hydroxyde gave the corresponding 2,3-epoxyamides 5, 8 and 10 , and the reaction of 1 , or 5- O -trityl-2,3- O -isopropylidene-D-ribofuranose 13 with N,N-diethylcarbamoylmethyl dimethyl sulphonium chloride and a 10–50% solution of sodium hydroxyde gave the corresponding 2,3-epoxyamides 4 and 14 , respectively, with high yields and variable stereoselectivity.

Unstabilized diazo derivatives from carbohydrates. Application to the synthesis of 2-deamino-tunicamine and products related to C-disaccharides

Abstract We applied a new synthetic method to C-disaccharides to obtain 2-deamino-tunicamine, the 2-hydroxy analogue of tunicamine, which is the main nucleus of tunicamycin antibiotics. 6-Deoxy-6-diazo-1:2,3:4-di-O-isopropylidene-D-galactopyranose was synthesized and reacted with methyl 2,3-O-isopropylidene-β-D-ribopentonodialdo-1,4-furanoside, to obtain a mixture of ketone and an epoxide with C-disaccharide structures. The epoxide was obtained in a reasonably good yield and full stereoselectivity, and was reduced to protected 2-deamino-tunicamine. Reduction of the ketone isomer, yielded the 7-epimer of 2-deamino-tunicamine. This is the first reported instance of an epoxy-C-disaccharide, the primary interest of which lies in its potential inhibition of glycosidase enzymes.

A New Synthesis of 2-C-Methyl-d-Ribono-1,4-Lactone and the C-9/C-13 Fragment of Methynolide

Abstract The synthesis of the glucosaccharino lactone, 2-C-methyl-D-ribono-1,4-lactone 7 from 2,3-O-isopropylidene-D-glyceraldehyde 1 is reported. Lactone 7 was transformed into (2R,3R)-2,3-dihydroxy-2-methylpentanoic acid 18 (the C-9/C-13 fragment of Methynolid) by two new procedures which improve on existing alternatives: conversion of the epoxide derivative 9 to the episulfide 14 and subsequent reduction; and reductive opening of the 5-bromo derivative of 2,3-O-isopropylidene-2-C-methyl-D-ribono-1,4-lactone and subsequent hydrogenation.

Stereoselective synthesis of 2,3-epoxy-amides by aldol-like condensation of 2,3-O-isopropylidene-D-glyceraldehyde with N,N-diethyl diazoacetamide

Abstract The 1:1 mixture of cis:trans epoxy-amides 5c was obtained quantitatively by condensation of 2,3-O-isopropylidene-D-glyceraldehyde 1 with N,N-diethyl diazoacetamide. Similarly, the reaction of 1 with methyl diazopropionate was studied and gave as the main product the β-ketoester 4b (product of a 1,2-hydrogen shift) and, in a low yield, the glycidic ester 5b (intramolecular nitrogen displacement). The configuration at C-3 of the resultant epoxides of both reactions revealed that the addition step was completely stereoselective. Under similar conditions, compound 6 , methyl 3-hydroxy-2-diazopropionate was unreactive, but with heating gave 7 .

β-Oxy-α-diazo carbonyl compounds. II: Conversion to chiral α-oxy-α'-diazo ketones and photochemical reaction

Abstract Chiral β-oxy-α-diazo methyl ketone was successfully converted to α-oxy-α′-diazo ketone in three steps. The photochemical reaction of this new diazo compound provides an improved synthesis of the 3-hydroxy-2-methyl carboxylate derivative 2 in threo relative configurations via a Wolff rearrangement. The influence of the protective group on the stereochemical result of the photochemical reaction is discussed.

Stereoselective synthesis of precursors of the macrolide antibiotics via reactions of sulfur ylides with chiral aldehydes

Abstract Reactions of stabilized sulfur ylides with chiral aldehydes provided epoxides with high stereoselectivity. The opening of the resulting epoxides with lithium dimethyl cuprate gave 2-methyl-3-hydroxy amides which represent potentially useful building blocks for the synthesis of macrolide natural products. These amides were transformed into chiral aldehydes, with a methyl group in the α-position, and were reacted, in a iterative process, with a sulfur ylide reagent to give, in high yield and stereoselectivity, the epoxides with the stereochemistry according to Felkin-Ahn control. Finally, opening of the epoxide with the Gilman reagent provided a compound with four stereocenters occurring in the macrolide-type of natural products.

β-Oxy-α-diazo carbonyl compounds. IV. Reaction with triethyl borane. The influence of the oxy group in the regio- and stereo-controlled alkylation on the diazo carbon

The reactions of chiral ~-oxy-ct-diazocarbonyl compounds with triethylborane were studied. The results of the reactions depend on the particular group used to protect the 13-hydroxyl function. Thus, hindered protecting groups lead to N-alkylation of the diazo compound. On the other hand, the product with a free hydroxyl group, undergoes C-alkylation in a good yield with full stereoselectivity.