Synthesis of unprecedented steroidal spiro heterocycles as potential antiproliferative drugs

Recent syntheses of steroidal oxazoles, oxazolines and oxazolidines

“…A straightforward methodology has been developed by Montiel-Smith and al. 35 to access the hitherto unknown spiro steroids bearing oxazolidin-2-one and 2-aminooxazoline motifs at C-17, starting from transandrosterone and estrone. The key intermediates were aminomethyl alcohols 66 and 67, which upon reaction with triphosgene, or with an alkyl/aryl isothiocyanate, followed by a cyclization, furnished title heterocyclic scaffolds (Scheme 9).…”

“…To prepare the ,-diol system on the steroidal side-chain, they chose 3-acetoxypregn-5-en-20-one (34) as starting compound (Scheme 14). Oxidation with Pb(OAc)4 in the presence of BF3•OEt2 furnished 3,21-diacetoxypregn-5-en-20-one (35). Reduction with KBH4 gave two compounds, 3,21-diacetoxypregn-5-en-20-ol 96a, and its 20 epimer, in a ratio of 9:1.…”

Recent syntheses of steroidal derivatives containing heterocycles

“…In 2018, Romero-Hernandez et al 60 reported the straightforward preparation of novel conformationallyrestricted steroids from trans-androsterone and estrone with spirocyclic oxazolidin-2-one or 2-aminooxazoline motifs at C-17 as potential antiproliferative agents. The key step to synthesize these heterocycles on the steroidal backbone was access to an aminomethyl alcohol on C-17 and its transformation into transient isocyanates and thioureas.…”

Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents

“…Based on the beneficial importance of these hybrid scaffolds, we moved our attention to the synthesis of steroidal pyrimidines in order to look for new antiproliferative compounds. We have previously reported some monomeric and dimeric steroidal triazolopyrimidine derivatives [13] and a family of steroidal spiro heterocycles from trans -androsterone and estrone bearing oxazolidin-2-one and 2-aminooxazoline motifs at C-17 [14]. A remarkable antiproliferative activity was found for some of the estrone derivatives with GI 50 values at the low micromolar level.…”