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Synthesis of 1 α‐ and 1 β‐amino‐25‐hydroxyvitamin D 3
Author(s) -
Akagi Yusuke,
Usuda Kosuke,
Tanami Tomoe,
Yasui Koji,
Asano Lisa,
Uesugi Motonari,
Nagasawa Kazuo
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600300
Subject(s) - chemistry , synthon , allylic rearrangement , diastereomer , amino acid , stereochemistry , sarcosine , ring (chemistry) , medicinal chemistry , catalysis , organic chemistry , biochemistry , glycine
Abstract 1α‐Amino‐25‐hydroxyvitamin D 3 is of interest because of its low calcemic effect in vivo compared to 1,25‐dihydroxyvitamin D 3 and its characteristic inhibitory activity towards sterol regulatory element binding protein (SREBP), a regulator of lipogenesis. Here we describe the construction of a novel A‐ring synthon bearing an allylic amine, in which the key reaction is an Ichikawa rearrangement of allyl cyanate generated from an allylic alcohol, which was derived from l ‐malic acid. The diastereomers were separated by silica‐gel chromatography, and a palladium‐catalyzed coupling reaction of each diastereomer with the CD‐ring synthon afforded 1α‐amino‐25‐hydroxyvitamin D 3 and 1β‐amino‐25‐hydroxyvitamin D 3 , respectively.