Design and synthesis of analogues of natural products

Abstract

In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error.

Biological Significance of Marine Actinobacteria of East Coast of Andhra Pradesh, India

“…are mostly obtained from natural products (Lam, 2007; Newman, 2008; Cragg and Newman, 2013; Newman and Cragg, 2016). By knowing their potent bioactivities, organic chemists have developed new drugs using modern advancements in synthetic biology (Beghyn et al, 2008; Maier, 2015; Rodrigues et al, 2016). …”

Diverted Total Synthesis of Carolacton-Inspired Analogs Yields Three Distinct Phenotypes in Streptococcus mutans Biofilms

“…We were inspired by the seminal work of Chandrasekhar et al in their disclosure of simplified pladienolide analogs wherein they rigidified the side chain with an aryl isostere and we determined that a similar replacement was feasible based on computational modeling (Figure 1). 17 We and others 18 have been drawn to this substitution as it would both simplify the synthesis and effectively evaluate the importance of the elaborate side chain. Herein, we report the DTS of 16 simplified carolacton-inspired analogs that have resulted in the discovery of three independent biofilm phenotypes: (1) inhibition of their formation, (2) inhibition of their maturation, and (3) acid-mediated cell death during formation, akin to carolacton, by an analog coined “carylacton”.…”

Which Ballast Water Management System Will You Put Aboard? Remnant Anxieties: A Mini-Review

“…Nevertheless, even though a myriad of natural bioactive substances are being discovered and published every year [78,79], natural biocide compounds are generally too complex to synthesize, and the greatest obstacle to producing green biocides at large scale and mass production levels are the technical challenges associated with developing practicable methods of synthesis that can scale to metric tonnes of output [80,81].…”