Novel double functional protection of cephalostatin analogues using a gas-free chlorination method. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Nawasreh, Mansour; Kirschning, Andreas; Duddeck, Helmut; Dräger, Gerald; Fenske, Dieter
• Is Part Of: Heliyon. Volume 6:Issue 1(2020)
• Publication Date: 2020-01
• Subjects: Natural product chemistry -- Organic chemistry -- Biochemistry -- Cancer research -- Cephalostatin 1 -- Chemo and regioselective transformations -- Gas-free chlorination method -- Double-functional protection; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2019.e03025
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: Herewith, we report on a method that allows to simultaneously protect both the ∆ 14, 15 bond and the carbonyl group of the symmetrical bis-steroidal diketone 2 . We found that environmentally friendly and gas-free chlorination is ideally suited to achieve this goal. This method was discovered during our efforts to methoxylate 2 in a solution of dichloromethane and basic methanol in the presence of diacetoxy iodobenzene. Unexpectedly, the ∆ 14, 15 bonds were chlorinated once as well as twice in a statistical manner. Interestingly, the singly dichlorinated desymmetrized product is an ideal precursor for conduction a series of position selective transformations. Importantly, the carbonyl group present in the nonchlorinated hemisphere can be selectively reduced, olefinated or oximated, while the other carbonyl group stays unaltered. A structurally related "monomeric" steroid derivative undergoes ∆ 14, 15 chlorination and 11-position methoxylation under same conditions. These findings represent a powerful entry for preparing new nonsymmetrical cephalostatin derivatives. Abstract : Natural product chemistry; Organic chemistry; Biochemistry; Cancer research, Cephalostatin 1; Chemo and regioselective transformations.; Gas-free chlorination method; Double-functional protection.