Studies toward the Synthesis of Potent Anti-inflammatory Peptides Solomonamides A and B: Synthesis of a Macrocyclic Skeleton and Key Fragment 4-Amino-6-(2′-amino-4′-hydroxyphenyl)-3-hydroxy-2-methyl-6-oxohexanoic Acid (AHMOA)

Abstract

A first synthetic effort toward total synthesis of highly potent solomonamides is disclosed. An efficient strategy to synthesize this class of compounds, along with the synthesis of a core macrocycle (shown in red) and the key fragment AHMOA, is described.

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.…”

Breaking and Making of Olefins Simultaneously Using Ozonolysis: Application to the Synthesis of Useful Building Blocks and Macrocyclic Core of Solomonamides

“…Solomonamide A, 1 , was reported to have shown very potent anti-inflammatory activity in mouse model at a very low concentration of 100 μg/kg and solomonamide B, 2 , could not be tested due to scarcity of the material Because of its interesting biological potential, it is now one of the major research projects in our group, and we have already made significant contributions to this project. , As of today, no total synthesis of solomonamides has been reported. However, three synthetic approaches have been disclosed in the literature including two from our group. − Chandrasekhar’s group prepared the nonpeptide key component of solomonamide A, 1 , starting from a readily available chiral building block .…”

Access to a Stereoisomer Library of Solomonamide Macrocycles

“…The alcohol 18 was converted into desired key unnatural amino acid 8 using Corey‐Schmidt condition (PDC/DMF) with 80 % yield (Scheme ). Further, to confirm stereochemistry of crotylated product 8 we attempted synthesis of five‐membered cyclic carbamate derivatives on 19 by treatment with 60 % sodium hydride in anhydrous THF for 12 h. In 1 H NMR the coupling constant for C4 and C3 attached proton shows 7.3 Hz which supported the stereochemistry of the 19 based on literature precedences (and previous report from our group) …”

“…Thus, aldehyde 7 a underwent NHK crotylation reaction using anhydrous CrCl 2 and trans ‐crotyl bromide in THF gave a 2:1 ratio of diastereomers 25 and 26 in 62 % yield (Scheme ) . All the spectral details of major diastereomer 25 were in complete agreement with its reported structure with stereochemistry as 2 S , 3 R , 4 R . Stereochemistry of minor compound 26 was assigned on the basis of the literature precedence .…”