Solid-Phase Total Syntheses of Trunkamide A and Kahalalide F, Cyclic Peptides from Marine Origin

Convergent Approaches for the Synthesis of the Antitumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

“…pNZ-Orn(Boc)-OH was prepared as described previously 29 and Alloc-amino acids as essentially described by Dangles et al and Cruz et al 37,38 Alloc-ZDhb-Phe-OH was prepared as before. 39 Solid-phase syntheses were performed in polypropylene syringes (10-50 mL), each fitted with a polyethylene porous disk. Solvents and soluble reagents were removed by suction.…”

“…p NZ-Orn(Boc)-OH was prepared as described previously 29 and Alloc-amino acids as essentially described by Dangles et al and Cruz et al . , Alloc- Z Dhb-Phe-OH was prepared as before …”

Chemistry and Biology of Kahalalides

“…The reductive alkylation of KF was best performed under optimized conditions by the exposure of parent molecule to 5 equiv of the known aldehyde in methanol for 30 min at room temperature prior to portionwise addition of 2 equiv of triacetoxyborohydride under the same conditions. The reaction time was designed from a few hours to a couple of days and gave the desired products (57)(58)(59)(60)(61)(62)(63) in good to very good yields (Scheme 5). Furthermore, one KF analogue (64) was simply synthesized by treatment of DEAC-carboxylic acid and KF (6) in the presence of EDC and HBTU in DMF at room temperature for 1 h.…”

“…Many review articles and patents on the kahalalides have appeared in the literature. 28-60 The initial discovery of KF ( 6 ) and its closely related isomer, isoKF ( 22 ), was first reported by Hamann and Scheuer in 1993. 14,15 In the course of the investigation of natural products from the mollusk E. rufescens and the alga B. pennata , the constituents were shown to be dominated by amino and fatty acid-derived depsipeptides.…”

Lysosome and HER3 (ErbB3) Selective Anticancer Agent Kahalalide F: Semisynthetic Modifications and Antifungal Lead-Exploration Studies

“…Because of the limited availability of the natural product, data regarding structure−activity relationship (SAR) studies of 1 have not been reported in the literature and remain limited to the data generated from isolated natural products, as well as solid-phase total synthesis reported for 1 . ,− In a continued investigation of biologically active marine natural products and their optimization using semisynthesis, we were particularly interested in structure−activity relationships of 1 analogues against opportunistic fungal infections of humans and plants. − …”