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.
Sakuda
S
S
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. asakuda@mail.ecc.u-tokyo.ac.jp
Sugiyama
Y
Y
Zhou
Z Y
ZY
Takao
H
H
Ikeda
H
H
Kakinuma
K
K
Yamada
Y
Y
Nagasawa
H
H
D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D002688:Chitinases / Q000037:antagonists & inhibitors*; D003903:Deuterium; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism; D014312:Trisaccharides / Q000096:biosynthesis* / Q000737:chemistry
D004791:Enzyme Inhibitors; D014312:Trisaccharides; C433386:allosamine; C442377:allosamizoline; C054851:allosamidin; D003903:Deuterium; D002688:Chitinases; D005944:Glucosamine; D000117:Acetylglucosamine