467218-05-9Relevant academic research and scientific papers
Asymmetric syntheses of the homalium alkaloids (-)-(S, S)-homaline and (-)-(R, R)-hopromine
Davies, Stephen G.,Lee, James A.,Roberts, Paul M.,Stonehouse, Jeffrey P.,Thomson, James E.
, p. 7028 - 7045 (2012/10/08)
The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine. The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (-)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4′R,4′′S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (-)-(R,R)-hopromine.
Enantioselective entry to the Homalium alkaloid hoprominol: Synthesis of an (R,R,R)-hoprominol derivative
Ensch, Corinne,Hesse, Manfred
, p. 233 - 246 (2007/10/03)
The diastereoselective synthesis of the N- and O-protected hoprominol derivative (R,R,R)-6 is described. The building up of the bicyclic O-silylated and di(N-tosylated) asymmetric scaffold 6 succeeded by convergent preparation of the two basic chiral azalactam units 7a and 7b and their subsequent iterative linking by a known method (Scheme 5). Both 4-alkyl-hexahydro-1,5-diazocin-2(1H)-ones 7a and 7b were prepared from the chiral β-amino acid portions 10a and 10b, respectively, by application of a set of reactions (e.g., N-alkylation of 10a,b and Sb(OEt)3-assisted cyclization of the resulting open-chain intermediates) already known. In comparison with the total syntheses of homaline (1) and homoprine (2), the newness of the described synthesis lies in the asymmetric approach to the difunctionalized fatty acid derivative 10b starting from (-)-(S)-malic acid (9) (Schemes 3 and 4). Key step in the preparation of 10b was the diastereoselective amination of the optically pure α,β-unsaturated δ-hydroxy homoallylic ester 14 via conjugate intramolecular aza-Michael cyclization of the acylic δ-(carbamoyloxy) intermediate 11.
Total syntheses of the spermine alkaloids (-)-(R,R)-hopromine and (±)-homaline
Ensch, Corinne,Hesse, Manfred
, p. 1659 - 1673 (2007/10/03)
The diastereoselective synthesis of the spermine alkaloid (R,R)-hopromine (2) is described. The as yet unknown absolute configuration of naturally occurring (-)-hopromine (2) is (R,R) and was established by comparison of the reported specific rotation of the natural product with that of the synthetic one. Preparation of the characteristic bis-8-membered lactam scaffold was carried out by convergent build-up of basic chiral azalactam units 21a and 21b and subsequent iterative linking (Schemes 5 and 6). Key steps in the analogous syntheses of 4-alkyl-hexahydro-1,5-diazocin-2(1H)-ones 21a and 21b were the introduction of the unbranched alkyl side chains into their common precursor 14 via cuprate reaction and the Sb(OEt)3-assisted cyclization of the open-chain intermediates 20a and 20b, respectively (Schemes 3 and 4). The chiral iodoester 14 was prepared from commercially available (+)-L-aspartic acid (12). Based on the synthetic strategy developed for (R,R)-hopromine (2), a rapid access to the parent alkaloid homaline (1) in its (±)-form is given.
