Alternative Access to Functionalized 2,8-Ethanonoradamantane Derivatives.

Pelayo Camps,Tània Gómez,Ane Otermin,Mercè Font-Bardia

doi:10.3390/molecules22060906

Abstract

7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn- and anti-alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn-stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process. Additionally, several functional 2,8-ethanonoradamantane derivatives have been prepared.

Highlights

Some time ago, the synthesis of the functionalized polycycle 13 as a new scaffold for the preparation of compounds with potential biological activity was described [1]
An alternative synthesis of polycycle 13 has been developed by using methoxymethyl, instead of benzyloxymethyl, as a hydroxyl-protecting group
The overall yield of both synthetic sequences is of the same order

Summary

Introduction

The synthesis of the functionalized polycycle 13 as a new scaffold for the preparation of compounds with potential biological activity was described [1]. Improvements of the synthesis of 13 were performed [2,3], the highly-optimized synthetic route to this compound is shown in Scheme 1. During purification of this compound, implying a sublimation process, the presence of a benzyl ester derivative, probably 14, in the non-sublimed residue was suggested by 1 H-NMR. To solve this problem, an alternative synthesis of polycycle 13 was planned in which the methoxymethyl hydroxyl-protecting group would be used instead of the benzyloxymethyl one (Scheme 2).

Methods

Discussion

Conclusion