No abstract

A general method for the homologation of aldehydes to a-amino aldehydes (aminohomologation) has been developed, which employs nitrones as iminium derivatives of the aldehydes. Key operations include a) the addition of a thiazole metalated at C-2 to the N-benzylnitrone derived from the aldehyde, b) the reductive dehydroxylation of the resultant thiazolyl N-benzylhydroxylamine, and c) the unmasking of the formyl group from the thiazole ring. The homologation sequence was studied by employing nitrones derived from various chiral polyalkoxy aldehydes and dialdoses. The addition of 2-lithiothiazole to these nitrones was synselective, whereas the reaction with the same nitrones precomplexed with Lewis acids was mri-selective. Hence, from each nitrone a pair of diastereoisomeric hydroxylamines was obtained. These compounds were then converted by the above sequence into a-epimeric a-amino aldehydes. Model elaborations of some of these products afforded the amino sugars D-glucosamine, D-mannosamine, D-nOJirimycin, and advanced intermediates for the synthesis of destomic acid and lincosamine.

A route to epimeric carbon-linked glycoglycines that exploits the stereoselective addition of 2-lithiofuran and 2-lithiothiazole to sugar nitrones has been described. The reaction occurs with opposite diastereofacial selectivity depending on whether the free nitrone or the diethyl aluminum chloride precomplexed derivative is employed. The resulting furyl or thiazolyl hydroxylamines are dehydroxylated to amines by the action of titanium(III) chloride. From these compounds the amino acids are revealed by the oxidative cleavage of the furan ring or by the conversion of the thiazole into the formyl group and oxidation to carboxylic acid. Compounds have been prepared wherein the α-amino acid moiety is installed at C-4 and C-1 of furanoses (ribo, manno, xylo, and lyxo) and at C-5 and C-1 of a pyranose (galacto).

A convergent synthesis of the peptidyl nucleoside antibiotic (inhibitor of chitin biosynthesis) polyoxin J (2) by coupling of 5-O-carbamoyl polyoxamic acid (3) and thymine polyoxin C (4) is described. These compounds were prepared by chain elongation and amination of sugar-derived aldehydes employing their nitrones as iminium derivatives and the furan ring as a masked carboxyl. Thus, the stereoselective addition of 2-lithiofuran to the l-threose derived N-benzyl nitrone 5 followed by reduction of the resulting hydroxylamine to amine, carbamoylation of the free hydroxy group, and oxidative cleavage of the furan ring to the carboxylate group gave a protected derivative of 3 (30%). The same method was followed for the synthesis of the ribofuranosyl α-amino acid nucleoside 4 (12.6%) starting from the d-ribose derived nitrone 6. The final coupling was performed by the N-hydroxysuccinimide active ester method in DMSO with the Hünig base (i-Pr2EtNH) using a derivative of 3 and unprotected 4.