Synthesis of the cyclic heptapeptide core of callipeltin A

Abstract

Macrolactonisation of a suitable heptapeptide precursor provides the cyclic depsipeptide core of callipeltin A in excellent yield.

Total Synthesis of Salviachinensine A Using a Matteson Homologation Approach

“…Due to our interest in the synthesis of natural products with anti‐cancer activity [2–4] we became interested in the synthesis of salviachinensine A by employing Matteson homologations to generate the stereogenic centers [5–8] . We recently used this approach in the synthesis of several polyketide‐peptide conjugates [9–12] . In general, alkylboronic esters A were used as the starting material and after reaction with deprotonated dichloromethane, the stereoselectively formed α‐chloroboronic ester B can be reacted with a variety of nucleophiles, such as Grignard reagents or alkoxides, to afford a modified boronic ester C ( Scheme 1 ,a ) [5–8] .…”

“…Based on our previous results, [9][10][11][12] we began our investigations with chiral boronic ester 1, which is easily obtained from the corresponding commercially available boronic acid and (R,R)-DICHED. [23,24] Under the previously optimized reaction conditions, LiCHCl 2 was generated from dichloromethane and n-BuLi at À 100 °C, and 1 was added in the presence of one equivalent ZnCl 2 (Scheme 3).…”

Rapid mild macrocyclization of depsipeptides under continuous flow: total syntheses of five cyclodepsipeptides

“…10,11 It is well known that the macrocyclization step is the key step in cyclodepsipeptide synthesis, especially in the macrolactamization of N-alkylated amino acids (N-methyl amino acids or proline) 12 and in macrolactonization. 13,14 It has been reported that the macrolactamization of N-alkylated amino acids has the potential to introduce cis-amide bonds into peptides and results in a turninducing isomer, 15,16 and the lower nucleophilicity of N-alkylated amine and hydroxy also leads to a lower yield of macrocyclization compared to the primary amine case. On the other hand, a sterically hindered amino acid will also affect the yield of linear precursors via solid-phase peptide synthesis (SPPS).…”

Matteson Homologation-Based Total Synthesis of Meliponamycin A

“…Unfortunately, in our hands these protocols suffered from low yields or poor stereoselectivities. Therefore, we developed an alternative Matteson homologation-based synthesis (Scheme ), an approach that we recently used for the preparation of some atypical amino acids found in callipeltin A. , Starting from isopropylboronic ester 7 , we obtained the prolonged α-chloroboronic ester after treatment with (dichloromethyl)­lithium, which we subsequently converted to 8 by substitution with NaOBn. After a second homologation, treatment with an excess of sodium azide in DMF afforded α-azido-β-(benzyloxy)­boronic ester 9 in excellent yield as a single stereoisomer.…”