Total Synthesis of Miuraenamides A and D

Abstract

Miuraenamides A and D, cyclodepsipeptides with antimicrobial and antitumor activity, were synthesized. The synthesis of an unsaturated hydroxycarboxylic acid moiety, starting from a chiral epoxide, was achieved by Suzuki-Miyaura coupling as a key step. As a result, the overall yield for miuraenamide A over the longest linear sequence is 3.2%, while the yield of the previously reported procedure is 1.9%. In addition, the cell growth-inhibitory activity and anti-Phytophthora activity of the synthesized compounds were evaluated.

Syntheses of Gibberellins A15 and A24, the Key Metabolites in Gibberellin Biosynthesis

“…The combined filtrates were concentrated under reduced pressure and the higher boiling point components azeotrophed with dry toluene (100 mL) to provide the crude acyl chloride 20 as a yellow oil, which was subjected to the next step directly. Step ii: The crude acyl chloride 20 obtained was dissolved in dry Et 2 O (50 mL) and added, dropwise, to a stirred solution of diazomethane in ether (170 mL of a 0.9 M solution in diethyl ether, prepared from the known literature procudure) at 0 °C. Upon completion of the addition, the solution was allowed to warm to 18 °C over 16 h. Careful evaporation of the excess diazomethane and removal of Et 2 O provided the crude diazoketone 21 as a yellow oil, which was subjected to next step directly.…”

“…The Journal of Organic Chemistry from the known literature procudure37 ) at 0 °C. Upon completion of the addition, the solution was allowed to warm to 18 °C over 16 h. Careful evaporation of the excess diazomethane and removal of Et 2 O provided the crude diazoketone 21 as a yellow oil, which was subjected to next step directly.Step iii: The obtained crude diazoketone 21 was dissolved in dry THF and cyclohexane (80 mL, 1:1 v/v) and added, dropwise, to a refluxing solution of bis(N-…”

Direct Synthesis of N-Protected Serine- and Threonine-Derived Weinreb Amides via Diboronic Acid Anhydride-Catalyzed Dehydrative Amidation: Application to the Concise Synthesis of ­Garner’s Aldehyde

“…To this end, a number of coupling reagents have been developed. 8 Recently, some condensation conditions using EDCI, 9 HBTU, 10 HATU, 11 CDI, 12 and T3P 13 as coupling reagents were applied to the synthesis of -hydroxy--amino acid derived Weinreb amides. However, these conditions require stoichiometric amounts of reagents, resulting in cumbersome workup and purification procedures and poor atom economy.…”

Turning the Actin Nucleating Compound Miuraenamide into Nucleation Inhibitors

“…Small actin-binding molecules can roughly be divided into two groups: destabilizers (like, e.g., latrunculin or cytochalasin D) and stabilizers (like, e.g., phalloidin or jasplakinolide). Miuraenamide A, a myxobacterial compound that has been identified and chemically characterized some years ago, , belongs to the group of nucleators and is quite well synthetically accessible. − Consequently, this compound has previously been used by us for derivatization to define a structure–activity relationship . Using an extensive computational approach, we have previously proposed a binding mode of miuraenamide, which explains its biological activity: miuraenamide binding ensures a tighter and stronger packing of the actin monomers compared to the apo F-actin by shifting the DNase-I binding loop (D-loop), which is indispensable for F-actin stabilization, thus promoting nucleation of actin monomers.…”