Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

Headnote

Keywords:

aminocyclitols; aminocyclooctanetriol; azides; aziridines; aziridinecyclooctanediol

Abstract

Cyclooctene endoperoxide was used as the key compound for the synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol. Reduction of the cyclooctene endoperoxide, prepared by photooxygenation of cis,cis-1,3-cyclooctadiene, with zinc gave a cyclooctenediol and then benzylation of the hydroxy group yielded dibenzylated cyclooctene. Oxidation of the latter compound by OsO₄/NMO followed by mesylation of the hydroxy group provided bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate. Reaction of the bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate with NaN₃ gave 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate. Reduction of the azide group and debenzylation to give an amine provided the new 3-aminocyclooctanetriol. Treatment of the 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate with Zn/NH₄Cl and debenzylation resulted in the target aziridinecyclooctanediol.

Introduction

Aziridines are the smallest nitrogen-containing heterocycles and they are important building blocks in the synthesis as well as substructures of a number of biologically active natural and unnatural products [1-8]. Aziridines are valuable synthetic intermediates for the preparation of structurally complex molecules because of their versatility in numerous regio- and stereoselective ring opening and/or expansion reactions, as well as rearrangements [5]. The aziridine structural motif is present in natural products such as mitomycins and azinomycins (Figure 1) [1,5], which exhibit potent biological activities such as antitumor and antibiotic activities.

Therefore, synthetic methodologies for the preparation of the aziridinyl system have attracted attention in recent decades. Opening of the aziridine ring by using different nucleophiles gives the corresponding amino alcohols, amino esters, azido amines, amines, and other derivatives [9]. Furthermore, aziridine derivatives are valuable precursors for the synthesis of aminocyclitols, which can be found in nature in several families of natural and clinically important antibiotics [10].

Aminocyclitols containing the amino alcohol motif are important structural components for modifying bioactive natural products and pharmaceuticals. Valienamine (3) and its analogues show inhibitory activity against certain glycosidases [11- 13] (Figure 1).

Many groups have described different synthetic methods for the synthesis of various aminocyclitols [13-17]. However, only few synthetic methods are available for the synthesis of eight-membered [18-29] aminocyclitols. On the other hand, the synthesis of a C8-cyclitol derivative containing the aziridine ring has not yet been reported. Therefore, in our continued efforts for efficient syntheses of cyclitols [30-33] and C8-aminocyclitols [18- 24], we were interested in developing an efficient synthesis of aziridinecyclooctanediol. In the present paper, we report...