Claude Thal

Synthesis of a rhazinilam analogue acting as an inhibitor of tubulin assembly

AbstractThe synthesis of a di-nor-secorhazinilam analogue is described. This phenylpyrrole compound has beenprepared by a Susuki cross-coupling reaction between 1,2,5 trisubstituted pyrrole halides and 2-N-(tert-butoxycarbonyl)aminophenyl boronic acid. In contrast to rhazinilam, this new phenylpyrrole inhibits theassembly of tubulin into microtubules. # 2000 Elsevier Science Ltd. All rights reserved. Keywords: rhazinilam; phenylpyrroles; coupling reactions; biological activity tubulin. (^)-Rhazinilam 1 is a natural tetracyclic compound possessing a phenylpyrrole subunit and anine-membered lactam ring. 1 It was found to act as an inhibitor of microtubules disassembly. 2 Aspart of a program 3 directed towards the synthesis of biaryls mimicking the structure of the anti-mitotic (^)-rhazinilam 1, we previously reported the synthesis of various ortho-bridged biphenyls(compound 2). 4,5 We showed that the replacement of the lactam (compound 2a) by an urethanefunction (compound 2b) increases the binding with tubulin and that the binding interaction isstereoselective.

Improved Syntheses of 2-Bromonicotinaldehyde and Acid

Abstract Synthetically useful 2-bromonicotinaldehyde and 2-bromonicotinic acid can be conveniently prepared in high yield from the directed ortho metalation of 2-bromopyridine.

Synthesis and Separation of New Dibenz[b,d]azonine Atropisomers

Abstract A synthesis of the dibenz[b,d]azonine atropisomers (14) from 2-phenylbenzoic acid is described. This heterocycle belongs to a new series of biaryl compounds with potential antitubulin activity.

New Synthetic Route to Pummerer's Ketone

Abstract Pummerers ketone 1 is obtained with an overall yield of 55 % by the following sequence: Claisen rearrangement of an arylcyclohexylether 3; allylic oxidation of the methylcycloalkylphenolic derivative 4b, then spontaneous cyclisation during demethylation to give 2. 1 is obtained by dehydrogenation of 2. NMR data agree with a cis stereochemistry at C4a and C 9b.