Synthetic approaches towards a new class of strained "lactenediynes"

Abstract

The paper described two alternative synthetic approaches towards a new class of strained "lactenediynes", compounds where a 10-membered enediyne ring is fused with a β-lactam. Although the two alternative syntheses were successful up to the last step, the cyclization to give the desired products failed in both cases, probably because of excessive steric strain in the products. In one of the two approaches (which was the most efficient one in terms of overall yield) a mixture of diastereoisomeric cyclodimers was isolated in moderate yield. A certain degree of stereoselectivity was observed. These compounds may be interesting as new supramolecular systems.

Dicobalt Hexacarbonyl Complexes of Alkynyl Imines in a Sequential Staudinger/Pauson−Khand Process. A Route to New Fused Tricyclic β-Lactams

“…These imines have been used as substrate in nucleophilic 1,2- or 1,4-additions . A limited number of Staudinger [2 + 2] cycloadditions are known. , Metal-catalyzed cycloisomerizations and hydrocarbonylations leading to nitrogen-containing heterocycles have been explored recently. To the best of our knowledge, only one article, dealing with cyclotrimerization, mentions the reactivity of their dicobalt hexacarbonyl complexes …”

Design, Synthesis, and Biological Activity of Unnatural Enediynes and Related Analogues Equipped with pH-Dependent or Phototriggering Devices

“…A few months after the publication of the propargyl sulfone work, Banfi and Guanti reported the first synthesis of β-lactam-fused enediynes 4.076 and 4.077 . − They have elegantly demonstrated that the β-lactam ring can act as a locking device to stabilize the otherwise unstable 10-membered enediyne system. Opening of the β-lactam ring unlocked the system, which enabled it to undergo BC.…”

“…Because of the importance of these enediynes, it is pertinent to briefly mention their synthesis in this review. In Banfi's method, the key step is an intramolecular addition of acetylene to an aldehyde involving the Nozaki reaction 80 (Scheme ).

21 Nozaki Reaction Route to Azetidinyl Enediyne (Banfi and Guanti) a a (a) Pd(PhCN) 2 Cl 2 , CuI, piperidine, THF; (b) (i) AgNO 3 , KCN; (ii) I 2 , morpholine, benzene, rt; (iii) (COCl) 2 , DMSO, NEt 3 , CH 2 Cl 2 ; and (c) CrCl 2 , NiCl 2 (cat.

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Design and synthesis of heterocycle fused enediyne prodrugs activable at will

“…More recently we have carried out two alternative approaches to structures (42). 23 In both cases, however, the final cyclization step failed to provide the desired monomer. In one case we could isolate various stereoisomeric cyclodimers.…”