Biosynthetic studies on the cyclopentane ring formation of allosamizoline, an aminocyclitol component of the chitinase inhibitor allosamidin

Allosamizoline (1) is an aminocyclitol component of allosamidin, a Streptomyces metabolite, and has a cyclopentane ring originated from D-glucosamine. Biosynthesis of the cyclopentane ring was studied by feeding experiments with a variety of deuterium-labeled glucosamine and glucose. In the feeding experiments with 3-(2)H]- and 4-(2)H]-D-glucosamine and 1-(2)H]-D-glucose, deuterium was incorporated into C-3, C-4, and C-1 of 1, respectively. On the other hand, feeding experiments with 5-(2)H]- and 6,6-(2)H(2)]-D-glucosamine showed that deuterium on C-5 and one of the two deuterium atoms on C-6 of glucosamine were lost during the cyclopentane ring formation of 1. In the feeding experiments with (6R)- and (6S)-6-(2)H(1)]-D-glucose, the (6R)-deuterium of glucose was incorporated into the proS position on C-6 of 1, but the (6S)-deuterium of glucose was not incorporated into 1. These results suggested that an intermediate with a 6-aldehyde group is involved in the biosynthesis of the cyclopentane ring moiety of 1 and overall inversion of stereochemistry of the C-6 methylene group occurred by stereospecific oxidation and reduction on C-6 during the formation of 1. The 6-aldehyde intermediate may play a key role in the biosynthetic step(s) of cyclization to form the cyclopentane ring and/or deoxygenation at C-5.