Asymmetric Total Synthesis and Stereochemical Revision of Gymnangiamide

Abstract

The asymmetric total synthesis of the originally proposed structure of gymnangiamide, a cytotoxic pentapeptide isolated from the marine hydroid Gymnangium regae Jaderholm, has been achieved. Key to the synthesis was the use of asymmetric hydrogenation of alpha-substituted beta-ketoesters through dynamic kinetic resolution for the preparation of nonproteinogenic chiral amino acids. The disparity of the NMR spectra between the synthetic material containing the L-serine residue and the natural product required a revision of the proposed structure.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…Other noteworthy examples of ATH-based DKRs in complex molecules syntheses that are not discussed in this Review are depicted in Figure . − …”

Marine natural products

“…597 Oxylipin 696, isolated by bioassay-directed fractionation (Sinularia numerosa, Kagoshima Prefecture, Japan), inhibited tube-formation in a human endothelial cell line model of angiogenesis. 603 A highly strained cyclo-1,3-carbazole structure 704 (antipathine A) was deduced for a metabolite isolated from the black coral Antipathes dichotoma (Sanya, Hainan Province, South China Sea). The meroterpenoid sarcophytonone 702, isolated from Sarcophyton crassocaule (Lingshui Bay, Hainan Province, South China Sea), also exhibited mild toxicity to Artemia salina.…”

“…601 Asymmetric synthesis of the originally proposed structure of the cytotoxic hydroid (Gymnangium regae) pentapeptide gymnangiamide 602 requires that the configuration of the terminal aguanidino-serine residue be reassigned from L-to D-as shown (703). 603 A highly strained cyclo-1,3-carbazole structure 704 (antipathine A) was deduced for a metabolite isolated from the black coral Antipathes dichotoma (Sanya, Hainan Province, South China Sea). 604 Cycloaplysinopsin C 705, a dimeric alkaloid isolated from the hard coral Tubastraea sp.…”

Transition‐Metal‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation: Sustainable Chemistry to Access Bioactive Molecules

“…We accomplished the first total synthesis and revision of the reported structure of gymnangiamide 44 ;28 a cytotoxic peptide isolated from the marine hydroid Gymnangium regae Jaderholm (Scheme ) 29. This pentapeptide contains three unusual amino acid residues, N ‐desmethyl dolaisoleucine (Ddil), O ‐desmethyl dolaproine (Ddap) and α‐guanidino‐ l ‐serine (Gser), in addition to (2 S ,3 S )‐isoleucine and (2 S ,3 R )‐phenylserine (Pser).…”