Conversion of dipeptides and a tetrapeptide to macrocyclic ionophores by means of caesium aided ring closure of the N-2-chloroacetyl derivatives

Abstract

Three di-, (Gly),, (Val), and (Leu),, and one tetra-peptide, (Gly),, have been acylated with 2-chloroacetyl chloride and the resulting products treated with Cs2C03 in dimethylformamide (DMF) solution; (Gly), and (Leu), provided strained 9-membered rings whereas (Val), dimerized to the 18-membered ring.

Macrolactonizations in the Total Synthesis of Natural Products

“…The usual conditions for these reactions are cesium or potassium carbonates in DMF or DMSO. This methodology has been applied to various syntheses of fluorolactones, ilalactones, keto-lactones, , 13−15-membered olfactive lactones, cyclodepsipeptides, exaltolide and ambrettolide, , taxanes A−B cycles, and the hemisynthesis of myxovirescine. It is also worthy of note that this procedure (potassium carbonate in DMSO) was found in a comparative study with other alcohol and acid activation methods to be the most efficient methodology to obtain a 10-membered lactone model (Scheme ) …”

Small depsipeptides as solvent gelators

“…During investigations of the synthesis and complexing properties of cyclic depsipeptides of the type shown (1-4), 1 we met with an unexpected phenomenon. Compound 1, cyclo[CH*-CO-L-Leucyl-leuci cine], is able to gelate the solvents diethyl ether, methylene chloride, ethyl acetate, acetonitrile and acetone.…”

Total Synthesis of Piperazimycin A: A Cytotoxic Cyclic Hexadepsipeptide

“…The methyl ester and acetyl protecting groups in 29 were carefully removed by saponification. When treatment of the resulting acid under reported reaction conditions (Cs 2 CO 3 , DMF, 80 8C), [22] the desired macrocycle could not be detected, and only decomposition of the acid was observed. Fortunately, when we treated this intermediate with NaI and K 2 CO 3 in DMF at 40 8C, we isolated the desired cyclization product 30 in 79 % yield.…”

“…The stage was now set for the crucial macrocyclization, and we planned to use a substitutive macrolactonization strategy which was initially reported by Kellogg and co-workers to close the macrocycle. [22] Accordingly, removal of the TBDPS ether in 28 afforded an alcohol, which was exposed to triphenylphosphine and hexachloroacetone (PPh 3 /HCA) [23] to provide chloride 29 in 89 % yield. The methyl ester and acetyl protecting groups in 29 were carefully removed by saponification.…”