Microwave-Assisted Concise Total Syntheses of Quinazolinobenzodiazepine Alkaloids

Abstract

[reactions: see text] One-pot total syntheses of the quinazolinobenzodiazepine alkaloids sclerotigenin (1), (+/-)-circumdatin F (2), and (+/-)-asperlicin C (3) via novel microwave-assisted domino reactions were achieved in 55%, 32%, and 20% yields, respectively, from commercially available starting materials. A two-step total synthesis of (+/-)-benzomalvin A (4) was accomplished with an overall yield of 16%. Additionally, analogues of circumdatin E were synthesized via the three-component one-pot sequential reactions promoted by microwave irradiation. Finally, a two-step formal total synthesis of (+/-)-asperlicin E (5) was also realized by using this microwave-assisted protocol.

A facial synthesis of quinazolino[1,4]benzodiazepine alkaloids via reductive N-heterocyclization of N-(2-nitrobenzoyl)amides: total synthesis of asperlicin C, circumdatin H, and its analogues

“…Furthermore, the naturally occurring asperlicin C 21,22,33,30 (1, Entry 4) was prepared from the reaction of 2-nitrobenzoyl chloride and tryptophan-derived benzodiazepine 4b 21,22,33,31 followed by hydrogenation.…”

“…15,16 Various methods for the synthesis of alkaloids encompassing a quinazolino [1,4]benzodiazepine moiety in their skeleton have been developed and numerous research papers and several reviews have recently appeared. 1,[17][18][19][20][21][22][23][24][25][26][27] The implementations of 2-azidobenzoylamides in aza-Wittig methodology 6,[28][29][30][31][32][33] and transition metalinduced reductive N-heterocyclization [34][35][36][37][38][39] have emerged as versatile strategies for the construction of a variety of heterocyclic compounds. Although the aza-wittig and metal-induced reductive cyclization procedures afford quinazolino [1,4]benzodiazepines, they have some disadvantages such as cost and availability of the reagents such as 2-azidobenzoyl chloride and transition metals, generation of phosphine oxide by-product, harsh reaction conditions, low atom economy and synthetic practicality.…”

Microwave-Assisted Natural Product Chemistry

“…This optimized, microwave-assisted, domino protocol was used for the synthesis of a variety of quinazolinobenzadiazepine alkaloid natural products [90]. The members of this broad family of naturally occurring alkaloids feature a broad spectrum of very intriguing biological potential: Sclerotigenin exhibits high anti-insectant activity, Aspercilin C and E show high Cholecystokinin (CCK) antagonist activity and Benzomalvin A features inhibitory activity against substance P at the neurokinin NK1 receptor [91,92].…”

Synthesis of a new tetracyclic ring system: pyrrolotriazepinoquinazolinone derivatives

“…11 Quinazolinobenzodiazepine alkaloids have been isolated from several fungus species. 12 Among these, benzomalvin A (4) exhibits potent inhibitory activity against substance P at the neurokinin NK1 receptor. 13 Moreover, many quinazolinone derivatives were synthesized exhibiting significant biological and pharmaceutical activities including antibacterial, 14 anticancer, 15e17 antihypertensive, 18,19 antiinflammatory, 20 antidiabetic, 21 and anticonvulsant 22 properties.…”