Scalable synthesis of the unusual amino acid segment (ADMOA unit) of marine anti-inflammatory peptide: solomonamide A

Abstract

The most abundantly available hexose sugar, d-glucose has been converted to protected 4-amino(2'amino-4'-hydroxy phenyl)-3,5-dihydroxy-2-methyl-6-oxo hexanoic acid (protected ADMOA, 3), the unusual amino acid present in marine natural product solomonamide A in gram quantities involving easy to operate chemical transformations.

Exploring the Antiangiogenic Potential of Solomonamide A Bioactive Precursors: In Vitro and In Vivo Evidences of the Inhibitory Activity of Solo F-OH During Angiogenesis

“…Therefore, in the particular case of the solomonamides, the scarce availability of T. swinhoei clearly conditioned the further characterization of the compounds’ bioactivities. In the last years, different studies toward the synthesis of solomonamides have been reported, mainly by Reddy et al [15,17,37,38,39,40,41]. In fact, very recently, the total syntheses of solomonamides A and B have been reported [13], which led to their stereochemical revision with respect to that initially proposed, and confirmed the anti-inflammatory activities reported for the natural products.…”

“…Thus, an extensive spectroscopic study allowed their structural determination, revealing the presence of three conventional amino acids ( d -Ala, Gly, and l -Ser) and an unprecedented 4-amino(2-amino-4-hydroxyphenyl)-3,5-dihydroxy-2-ethyl-6- oxohexanoic acid (ADMOA) and its corresponding 5-deoxy derivative (AHMOA) for solomonamides A and B, respectively. These peptide structures provide protection against peptidases and constitute a scaffold for new compounds with better biological activities [14,15].…”

Access to a Stereoisomer Library of Solomonamide Macrocycles

“…[3] Since last few years several groups are working on this target owing to its interesting structural features and having high potency as antiinflammatory compounds. [4][5][6][7] Recently,w eh ave reported total synthesis and stereochemical revision of both the natural products ( Figure 1). [7] Movingf orwardt owards the complete SSARs studies in systematic manner,w ed ecided to synthesize all the eight stereoisomericm acrocycles( without considering alanine stereochemistry at this point) to check the role of stereochem-istry in the bioactivity.A dditionally,t he study can provide the ways to construct these different stereoisomers using modification of chemical methods.…”

Exploring the Ring-Closing Metathesis for the Construction of the Solomonamide Macrocyclic Core: Identification of Bioactive Precursors

“…In fact, the anti-inflammatory activity of solomonamide B ( 2 ) was not evaluated due to limited amounts. The unique and unprecedented structures of the solomonamides, together with their intriguing biological properties, have generated intense synthetic activity . For example, the Reddy group has recently reported a total synthesis of a deoxy analogue of solomonamide B together with an array of simple unfunctionalized analogues, culminating with a total synthesis of the natural solomonamide B, which has led to a revision of the initially proposed structure as will be detailed later.…”