Synthesis of 3,5-disubstituted-1,2-dioxolanes: access to analogues of mycangimycin and some rearrangement products

Abstract Mycangimycin is a eicosa-heptenic acid containing an unprecedented 3,5-disubstituted-1,2-dioxolane ring with promising anti-fungal and antimalarial activity. Most reported methods to prepare 1,2-dioxolanes are targeting 3,3,5,5-tetrasubstituted or 3,3,5-trisubstituted 1,2-dioxolanes. Thus, some methods for synthesizing these unusual 3,5-disubstituted 1,2-dioxolanes were investigated. The most promising approach was the use of a Kulinkovich reaction followed by an oxidative ring opening of the cyclopropanol with Co(acac) 2 to reach the peroxy-hemiketal structure. Successive triflic acid mediated silane reduction of the corresponding peroxy-hemiketal afforded the expected 3,5-disubstituted-1,2-dioxolane ring. Through our studies, some unprecedented rearrangements of 1,2-dioxolane rings were observed, which will be discussed in this Letter. Finally, two saturated analogues of mycangimycin were synthesized.