Synthese eines cyclischen Depsipeptides mittels Amidcyclisierung

Abstract

Synthesis of a Cyclic Depsipeptide via an Amide Cyclization The synthesis of (S)‐Pms‐(R)‐Pro‐(S)‐Ala‐Aib‐N(CH3)2 (12) has been achieved according to Scheme 3. For the formation of fragment 11, the reaction of Z‐alanine (Z = benzyloxycarbonyl) and 3‐dimethylamino‐2,2‐dimethyl‐2‐azirine (1) has been used, whereby 1 serves as an aminoisobutyric‐acid dimethylamide (aib‐N(CH3)2) equivalent. Treatment of a suspension of 12 in toluene with HCl gas at 100° led to the cyclic depsipeptide 13 in 72% yield (Scheme 4). In presence of water, the acid 14 was isolated as the sole product. A mechanism for the formation of 13 and 14 via an oxazolinone intermediate, is postulated in Scheme 4.

Synthesis of a Regular 24-membered Cyclodepsipeptide by Direct Amide Cyclization

“…According to GP 12,18,3,9,9,15,15,21,7,13,10,16,5,8,11,14,17,20, Dry HCl gas was bubbled through a solution of 15 (300 mg, 0.31 mmol) in toluene (30 mL) at 100 • C for 4.5 min. The mixture was then heated under reflux for 20 min while a gentle stream of dry HCl gas was bubbled through the solution.…”

Synthesis of Z‐Protected Aib‐ and Phe(2Me)‐Containing Pentapeptides and Their Crystal Structures

“…One of the peptide molecules has a disordered Ph ring in the Z group. Two sets of positions were defined for the atoms of this Ph ring and the site occupation factor of the major conformation of the ring refined to 0.504 (1).…”

“…Introduction. -Since the elaboration of the 'azirine/oxazolone method' as a convenient protocol for the synthesis of Aib-containing peptides [1][2][3], this procedure has been used successfully for the preparation of model peptides [2c] [3][4][5][6], sterically congested oligopeptides [7] [8], and peptaibols [2d] [9][10][11]. It has also been shown that the method can be adopted to solid-phase methodology [12].…”

An Unexpected Formation of a 14‐Membered Cyclodepsipeptide

“…In the last few years, the number of reports on the use of macrolactonizations in the preparation of cyclodepsipeptides has increased remarkably [6][7][8][20] [21]. A useful method for the ring closure of depsipeptides which contain α,α−disubstituted α−amino acids is the so-called 'direct amide cyclization' method, developed in our laboratory [22][23][24][25][26][27][28]. The basic concept is that an amide of type 1 in a toluene solution or suspension is treated with dry HCl gas.…”