Ring formation, lactam

Lactam ring formation is observed in the rhodium-catalyzed ring-opening carbonylation of cyclopropylamine 20 to N-cyclopropylpyrrolidone 21 (Scheme 8) [14]. (Scheme 8)... 

A complete study of the basic hydrolysis of pyrazolidinone (196) by ab initio calculations at RHF/6-31+GV/RHF/6-31-fG" and MP2/6-31-bGV/MP2/6-31- -G levels has been carried out. The alkaline hydrolysis has been studied through a Z ac2 mechanism, characterized by a nucleophilic attack of the hydroxyl group on the carbonyl of the y-lactam ring, formation of the tetrahedral intermediate, and cleavage of the C(2)-N(3) bond to yield the final reaction product. ... 

The majority of cyclic peptides synthesized on solid support are cyclized in the head-to-side-chain or side-chain-to-side-chain mode. For this purpose the amino acids involved in cyclization must be side-chain protected in a manner that allows for an additional level of orthogonal deprotection. Thus, upon assembly of the fully protected linear precursor on-resin, deprotection of the functionalities involved in the lactam ring formation is performed, followed by regio-selective cyclization by amide bond formation, and finally by the resin-cleavage/deprotection step as outlined in Scheme 16. In Table 8, examples of syntheses of such cyclic peptides are listed with the relevant information regarding protection scheme, resin anchor, and mode of cyclization. 

Protection of an amino group by an electron-withdrawing group is not required particularly for energetically favorable lactam ring formation (Table 13). ... 

The lactam ring formation is elucidated by intermediacy of 221 and 222. In the absence of DBU, the lactam formation suffers from lack of reproducibility in yields and loss of (Z)-selectivity at the silylmethylene moiety (Equations (39) and (40)). " ... 

Lactam, ring formation, 288 Lactones, optically active, 31 Lanthanide complexes epoxy ring opening, 234 hetero-Diels-Alder reactions, 217 nitno-aldol reaction, 228 Laudanosine, 36 Leucine hydrocarboxylation, 168 Lewis acid complexes, 212 Ligands ... 

Dihydroazete 1-oxides, synthesis and reactivity 90BSF704. Four-component condensation in the synthesis of /3-lactams 91MI19. /3-Lactam ring formation 92YGK112. 

Isopenicillin-N synthetase mononuclear iron 0 -lactam ring formation 3.2.2. 

A review of approaches to the design and synthesis of azabicycloalkane amino acids as constrained dipeptide mimetics has been reported. These approaches include 7-membered lactam ring formation by free radical cyclization from a substituted proline precursor <04SL1449>. 

Serine is the precursor of several antibiotics. The oxazole ring of the antibiotic virginiamycin Mj 100(Scheme 31)is derived from serine incubation of Streptomyces virginiae with samples of (2S, 3R)- and (2S, 3S)-[3- Hi]serine, derived as in Scheme 18, showed that the 3-pro-S hydrogen of serine is lost on formation of the double bond (107). This implies anti dehydrogenation, a process more commonly found to be syn. The -lactam antibiotic nocardicin 101 is biosynthesized from serine, and incubation of Nocardia uniformis with stereospecifically deuterated serines, prepared by the method outlined in Scheme 21, has yielded samples of norcardicin, the NMR spectra of which indicated that ) -lactam ring formation occurs with inversion of configuration (108, 109). 

A retro-Michael reaction to open the pyrrolidine ring and undesired lactone or lactam ring formation were some of the side reactions (21b-c). In order to avoid unproductive pathways, Sakaguchi and coworkers discovered that bulky heptamethyldisilazane in large excess could provide the desired product 21a reproducibly in 50% yield. Phenol 21a was subsequently dibrominated and converted to amathaspiramide F in three steps. 

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