Pyridinium salt photochemistry in a concise route for synthesis of the trehazolin aminocyclitol, trehazolamine.
[reaction: see text] A strategy for the concise synthesis of trehazolamine, the aminocyclitol core of the potent trehalase inhibitor trehazolin, has been developed. The methodology takes advantage of photocyclization reaction of 1-methoxyethoxymethyl-3-pivaloxymethylpyridinium perchlorate to generate a bicyclic-aziridine intermediate, which is transformed under aziridine ring opening conditions to the key intermediate, 3,5-diacetoxy-3-pivaloxymethyl-4-(N-acetylamino)cyclopentene. In addition, the strategy is used in an enantio-divergent sequence for preparation of the natural (+)-trehazolamine and its unnatural (-)-enantiomer. In this route, the chiral auxiliary containing 1-(tetracetyl-alpha-D-glucosyl)-3-pivaloxymethylpyridinium perchlorate undergoes photocyclization to generate separable, diastereomeric bicyclic-aziridines, which are then independently transformed to enantiomeric 3,5-diacetoxy-3-pivaloxymethyl-4-(N-acetylamino)cyclopentenes.
Feng
Xiaohua
X
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Duesler
Eileen N
EN
Mariano
Patrick S
PS
D001388:Aziridines / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D003500:Cyclization; D004187:Disaccharides / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D015394:Molecular Structure; D010777:Photochemistry; D011726:Pyridinium Compounds / Q000737:chemistry; D012492:Salts / Q000737:chemistry; D013237:Stereoisomerism; D014198:Trehalase / Q000037:antagonists & inhibitors
D001388:Aziridines; D001643:Bridged Bicyclo Compounds; D004187:Disaccharides; D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds; D012492:Salts; C071816:trehazolin; C033132:aziridine; D014198:Trehalase