Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A

Abstract

A biosynthetic hypothesis proposed herein was used to guide the total synthesis of the marine-derived alkaloid hyrtioseragamine A. In the key biomimetic step, an enedione underwent acid-mediated isomerization–cyclodehydration to form the rare furopyrazine core of the natural product. The spectroscopic data for the synthetic sample is in full agreement with that described in the isolation report.

Marine natural products

“…484 Two separate groups have reported the total synthesis of various oxo-aplysinopsin alkaloids. 485,486 Other compounds that have been synthesised include hyrtioseragamine A, 487 7-hydroxylamellarin A, 488 and ma'edamines C and D. 489 Three Dysidea-derived merosesquiterpenoids have been synthesised, 490 while three groups have independently revised the structure of dysiherbol A to 1167; the latter two groups also report the total synthesis of dysideanone B. [491][492][493] The structure of halioxepine 1168 has also been revised following its synthesis, 494 while the structures of diterpenoid metabolites cyclobutastellettolide B and hamigeran M have been conrmed following their rst total syntheses.…”

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…All these features make CDPs an attractive choice as biocompatible, green, functionalizable, and cheap building blocks for smart materials with a wide scope of applications from industry to medicine. The basic design is very simple: two amino acids bound together in a cyclic structure with a defined stereochemistry (i.e., LL, LD/DL, or DD) and the possibility to further derivatize the side chains [ 42 , 43 , 44 , 45 , 46 ] of selected amino acids [ 47 , 48 , 49 , 50 ], as widely applied in nature [ 51 , 52 , 53 , 54 , 55 , 56 ].…”

Rapid Total Synthesis of Iheyamine A via a Pictet–Spengler/Redox-Mediated Cyclization Cascade

“…To explore the cascade sequence of our proposal, we began synthesis studies toward the azepinobisindole core of iheyamine A ( 1a ). Accordingly, commercially available tryptamine 3 and easily prepared (2-nitrophenyl)-glyoxal 4a were adopted as the starting material, the acidic conditions for the Pictet–Spengler reaction were examined to initiate the domino sequence, and several reducing agents such as S, Fe, Zn, tetrahydroxydiboron, and PhSiH 3 were screened to achieve the selective reduction of hypothetical amine N -oxide. After several attempts (Table , entries 1–6), we were pleased to see that using both Fe powder and PhSiH 3 in AcOH solvent could respectively give the desired product in 56% and 52% yields.…”