76528-88-6Relevant academic research and scientific papers
β-lactams as building blocks in the synthesis of macrocyclic spermine and spermidine alkaloids
Wasserman, Harry H,Matsuyama, Haruo,Robinson, Ralph P
, p. 7177 - 7190 (2007/10/03)
Syntheses of the macrocyclic spermidine alkaloids (±)-celacinnine (1) and (±)-dihydroperiphylline (2) as well as the related spermine alkaloid (±)-verbascenine (3) were accomplished by means of sequential ring expansions of smaller lactam rings. Three ring expansion methods were employed: (1) transamidation of N-(aminoalkyl)lactams, (2) β-lactam-lactim ether condensation followed by reductive cleavage of the bicyclic 4-oxotetrahydropyrimidine product with NaBH3CN/AcOH and (3) bicyclic acyl hydrazine formation followed by N-N bond cleavage with Na/NH3. Each synthesis features ring expansion of a 4-phenylazetidin-2-one intermediate that undergoes transamidative ring expansion or lactim ether condensation.
Study of the Transamidative Ring Expansion of N-ω-Halogenoalkyl-β-lactams of Alkyl Chain Lengths 2-12 in Liquid Ammonia and Other Liquid Amines: Syntheses of 7-, 8- and 9-Membered 1,5-Diaza Cyclic Ketones, including Routes to (+/-)-Dihydroperiphylline and (+/-)-Celabenzine
Begley, Michael J.,Crombie, Leslie,Haigh, David,Jones, Raymond C. F.,Osborne, Steven,Webster, Richard A. B.
, p. 2027 - 2046 (2007/10/02)
N-(3-Halogenopropyl)-4-phenylazetidin-2-ones undergo amination in liquid ammonia followed by transamidative ring expansion to give the eight-membered 4-phenyl-1,5-diazacyclooctan-2-one in excellent yield.Ring expansion of the amines in liquid ammonia is found to be much more effective than in hydrocarbon solvents.Formation of 7-, 8-, and 9-membered azalactams from the requisite ω-halogenoalkyl-β-lactams is an excellent synthetic process, though it is not applicable to 10-membered rings.In the case of rings of 13-, 15- and 17-members, although amination and apparent expansion takes place, the large rings appear not to be stable to ammonia and the final products are acyclic amides.N--4-phenylazetidin-2-one satisfactorily forms a 9-membered (Z)-olefinic azalactam, but the (E)-isomer gives an acyclic amino amide.By using alkyl-substituted β-lactam side-chains, C-substituted medium rings can be obtained; the relative instability of N-acyl β-lactams to ammonia, however, leads to acylamino amides rather than expanded rings.Employing ethylamine in place of ammonia, it is shown that N-ethylated azalactams are formed satisfactorily, and using allylamine, N-allyl medium rings capable of further elaboration are obtained.The chemistry of these systems is discussed.Using transamidation in liquid ammonia, a short synthesis of the 9-membered spermidine alkaloid (+/-)-dihydroperiphylline is reported.Synthesis of key intermediates, whose transformation into the 13-membered alkaloids of the celabenzine group has already been effected, has been carried out.X-Ray single-crystal structure determinations for 4-phenyl-1,5-diazacyclononan-2-one, trans-4-phenyl-8-methyl-1,5-diazacyclooctan-2-one and (Z)-4-phenyl-1,5-diazacyclonon-7-en-2-one are reported, and comment is made on certain conformational features.
NEW APPROACHES TO THE SYNTHESIS OF SPERMINE AND SPERMIDINE ALKALOIDS
Wasserman, Harry H.,Robinson, Ralph P.
, p. 279 - 288 (2007/10/02)
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.
TRANSAMIDATION REACTIONS IN THE FORMATION OF MACROCYCLIC LACTAMS. A TOTAL SYNTHESIS OF CELLACINNINE.
Wasserman, Harry H.,Robinson, Ralph P.,Matsuyama, Haruo
, p. 3493 - 3496 (2007/10/02)
The macrocyclic spermidine alkaloid, cellacinnine, has been synthetized by methods involving successive ring expansion reactions.One route starts with 4-phenyl-2-azetidinone; another, with piperidazine.
