Synthesis and bioactivity of fused- and spiro-β-lactone-lactam systems

Abstract

An investigation of the formation of fused- and spiro-β-lactone annulate to γ-lactams has shown that the fused systems are formed preferentially, under standard conditions, but that spiro systems are accessible only when the formation of the fused system is blocked and require careful optimisation of reaction conditions. These systems display both weak antibacterial activity and proteasome inhibition.

Asymmetric Total Synthesis of (+)‐Neooxazolomycin Using a Chirality‐Transfer Strategy

“…Since the isolation of (+ +)-neooxazolomycin (1;S cheme 1) in 1985, [1] an umber of members of this family have been identified, including oxazolomycins A-C, [2] oxazolomycin A2, bisoxazolomycin A, [3] 16-methyloxazolomycin, [4] curromycins Aa nd B, [5] KSM-2690 B-C, [6] and lajollamycins A-D. [7] These oxazolomycins exhibit aw ide range of potent antibacterial and antiviral activities as well as in vivo antitumor activity. [9] However,t here are only af ew reports on the successful total syntheses of oxazolomycins. [9] However,t here are only af ew reports on the successful total syntheses of oxazolomycins.…”

Functionalised Nitrogen Heterocycles and the Search for New Antibacterials and Bioactives

“…The reversibility of the intramolecular aldol reaction was also found to be problematic (Scheme 6). 81,82 This type of intramolecular aldol reaction has been shown to have value in natural product synthesis (Figure 3). Oxazolomycins 54a-d and curromycins 54e,f, and the close analogue, neooxazolomycin, all complex natural products, 83 have been the focus of a large amount of attention over the last decade, and a ring-forming aldol reaction has been elegantly exploited in several syntheses.…”

Asymmetric Total Synthesis of Oxazolomycins B and C

“…[5,6] Their interesting bioactivities have been proposed to arise from their protonophoric properties [7] and structural similarity with the pharmacophore of salinosporamide A and omuralide. [8] Because of their structural complexity and potent biological activities, considerable efforts have been made toward synthesis. [5,9,10] However, only oxazolomycin A (1), neooxazolomycin (2), and lajollamycin B (8) have been successfully synthesized thus far.…”

“…[8] Because of their structural complexity and potent biological activities, considerable efforts have been made toward synthesis. [5,9,10] However, only oxazolomycin A (1), neooxazolomycin (2), and lajollamycin B (8) have been successfully synthesized thus far. [10] Kende et al achieved the first total synthesis of neooxazolomycin in 1990.…”

“…While neooxazolomycin ( 2 ) has a bicyclic γ‐lactone‐γ‐lactam core, the other members of the oxazolomycin family commonly have a spiro‐β‐lactone pyroglutamate core and exhibit wide‐ranging antibacterial and antiviral activities as well as in vivo antitumor activity [5,6] . Their interesting bioactivities have been proposed to arise from their protonophoric properties [7] and structural similarity with the pharmacophore of salinosporamide A and omuralide [8] …”