Synthesis of Polyamine Alkaloids by the Condensation of a Chiral β-Lactam with a Cyclic Imino Ether. (S)-Dihydroperiphylline and Its Derivatives

Abstract

The synthesis of 13-membered polyamine alkaloid, (S)-dihydroperiphylline, was achieved by the condensation of a chiral β-lactam, (S)-4-phenyl-2-azetidinone, with a cyclic imino ether of a 9-membered lactam, followed by reductive ring expansion. Both of these reactions proceeded with retention of configuration around the chiral center to give the optical pure 13-membered alkaloids.

Convenient Approach to 10‐ and 11‐Membered Azalactams

“…Continuing our study in this direction, we paid attention to a number of publications [21][22][23][24][25]28,29] highlighting the synthesis of macrocyclic polyamine alkaloids, with the key step being reductive ring-expansion of bicyclic derivatives of 4-oxotetrahydropyrimidine 1 (Scheme 1, R=Ar). The reduction of bicycles 1 was carried out with sodium cyanoborohydride in acetic acid.…”

Ruthenium‐Catalyzed Asymmetric Epoxidation of Olefins Using H2O2, Part I: Synthesis of New Chiral N,N,N‐Tridentate Pybox and Pyboxazine Ligands and Their Ruthenium Complexes

“…[26c, 27,47] However, rac-14 b and rac-14 c could not be resolved by this method. Therefore, we applied enzymatic resolution protocols for these substrates.…”

Conjugate addition of 6-membered hydrazine to chiral tert-butyl (E)-2-(p-tolylsulfinyl)cinnamates. Synthesis of (S)-celacinnine

“…The conjugate addition-cyclization reaction of piperidazine (5) to the optically active vinyl sulfoxide (S )-4 proceeded smoothly under basic conditions using potassium tert-butoxide in THF at room temperature to give the bicyclic compound 10, but the elimination of toluene-p-sulfenic acid ( p-TolSOH) from Scheme 1 10 occurred during its purification using column chromatography on silica gel, to give the unsaturated lactam 11 (Scheme 3).…”

“…Recently, the synthesis of a 13-membered lactam alkaloid, (S )-(ϩ)-dihydroperiphylline 2, starting from (S )-(Ϫ)-β-phenylβ-alanine, has been reported. 4, 5 Asymmetric synthesis of βamino acid derivatives using chiral vinyl sulfoxides has also proven to be useful methodology for the synthesis of chiral compounds. 6 Davis et al reported the diastereoselective synthesis of β-amino esters by addition of enolate ions to chiral sulfinimines.…”