- Asymmetric syntheses of the homalium alkaloids (-)-(S, S)-homaline and (-)-(R, R)-hopromine
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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.
- Davies, Stephen G.,Lee, James A.,Roberts, Paul M.,Stonehouse, Jeffrey P.,Thomson, James E.
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experimental part
p. 7028 - 7045
(2012/10/08)
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- Asymmetric synthesis of 4-phenyl-1,5-diazacyclooctan-2-one using optically active vinyl sulfoxides
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Both enantiomers of (S)- and (R)-4-phenyl-1,5-diazacyclooctan-2-ones (7) were synthesized stereoselectively with good optical purity by the asymmetric conjugate addition of pyrazolidine to optically active vinyl sulfoxides, t-butyl (E)-2-[(R)- and (S)-p-tolylsulfinyl]cinnamates, respectively. Starting from 7, a synthesis of optically active homaline was achieved.
- Itoh,Matsuyama,Yoshida,Kamigata,Iyoda
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p. 3121 - 3130
(2007/10/03)
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- Synthesis of the Alkaloid Homaline in (+/-) and Natural (S,S)-(-) Forms, using Amination and Transamidative Ring Expansion in Liquid Ammonia
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Synthesis of the alkaloid homaline in (+/-) and natural (S,S)-(-) forms is reported.Linking of 2-azacyclooctanone units either directly or successively using 1,4-dihalogenobutanes or 1,4-dihalogenobut-2-ynes is examined. (+/-)-5-Methyl-4-phenyl-1,5-diazacyclooctan-2-one is first made by a 2,2'-dithiodipyridine/triphenylphosphine-mediated cyclisation, and then by amination and transamidative ring expansion from N-(3-chloropropyl)-4-phenylazetidin-2-one in liquid ammonia, followed by N-methylation.Coupling through a 1,4-dihalogenobutane of either the N-methylated azalactam, or the unmethylated azalactam followed by methylation, gave homaline in (+/-) and meso forms. (R)-(-)-Phenylglycine was converted via (S)-β-phenyl-β-alanine into an (S)-β-lactam which was then alkylated with 1-bromo-3-chloropropane, and aminated and ring expanded in liquid ammonia.Coupling of the homochiral azalactam (2 mol) so formed with 1,4-dibromobutane, followed by N-methylation, gave (S,S)-(-)-homaline identical with the natural material.
- Crombie, Leslie,Haigh, David,Jones, Raymond C. F.,Mat-Zin, Ab. Rasid
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p. 2047 - 2054
(2007/10/02)
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- NEW APPROACHES TO THE SYNTHESIS OF SPERMINE AND SPERMIDINE ALKALOIDS
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New approaches to the formation of macrocyclic lactams are described involving successive ring expansion of 8-lactams and other heterocyclic systems.These methods have been used in the synthesis of a number of spermine and spermidine alkaloids including homaline, celacinnine, dihydroperiphylline, chaenorhine and verbascenine.
- Wasserman, Harry H.,Robinson, Ralph P.
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p. 279 - 288
(2007/10/02)
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- THE USE OF β-LACTAMS IN THE SYNTHESIS OF SPERMINE AND SPERMIDINE ALKALOIDS. TOTAL SYNTHESIS OF HOMALINE
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The optically active plant product homaline (6) has been synthesized in a convergent sequence starting with β-phenyl-β-alanine and putrescine (14).The key transformation in this sequence is the ring expansion by transamidation of a functionalized chiral β-lactam precursor.
- Wasserman, Harry H.,Berger, Gregory D.
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p. 2459 - 2464
(2007/10/02)
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- TRANSAMIDATION REACTIONS USING β-LACTAMS. THE SYNTHESIS OF HOMALINE
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The synthesis of the plant product, homaline, by a translactamization process involving the β-lactam, (-)-4-phenyl-2-azetidinone, is described.
- Wasserman, Harry H.,Berger, Gregory D.,Cho, Kathleen R.
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p. 465 - 468
(2007/10/02)
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