Pyridinium Salt Photochemistry in a Concise Route for Synthesis of the Trehazolin Aminocyclitol, Trehazolamine

Abstract

[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.

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…[114] Ein alternativer Weg, Intermediate des Typs 68 in enantiomerenreiner Form zu erhalten, besteht darin, N-substituierte Pyridiniumionen einzusetzen, wobei der Substituent als Auxiliar dient. [115] Eine Anwendung findet sich in der formalen Synthese des hexaacylierten (+)-Trehazolamins, [116] dessen Umwandlung in (+)-Trehazolin bekannt ist. [117] Ein Nalkyliertes Pyridiniumsalz diente als Vorstufe in einer formalen Totalsynthese des (À)-Cephalotaxins.…”

Ring Opening of 6‐Azabicyclo­[3.1.0]hex‐3‐en‐2‐ols in Water under Mild Conditions

“…Literature overview of ring-opening reactions of aziridines with S-nucleophiles in aqueous media. [17] The nucleophilic ring-opening reaction of bicyclic aziridines photoproducts has been explored under acid catalysis in the presence of several nucleophiles to afford trans,trans-3,5-disubstituted 4-aminocyclopentenes in moderate to good yields ( Table 2). [b] n.d.: not detected.…”

Applications of Chiral Three-membered Rings for Total Synthesis: A Review

“…In 2005, a photocyclization reaction providing chiral aziridines was developed by Mariano et al, starting from chiral pyridinium perchlorate 46 derived from D-glucose [32]. Irradiation of this substrate in aqueous NaHCO 3 produced a mixture of isomeric Nglycosyl-bicyclic-aziridines, which could be partially separated by chromatography to yield the major aziridine 47 (Scheme 21) as the only detected stereoisomer in 15% yield.…”