Enantioselective Total Synthesis of (+)-Nocardioazine B

Abstract

In this paper, we report an enantioselective total synthesis of (+)-nocardioazine B, a prenylated hexahydropyrrolo­[2,3-b]­indole (HPI) alkaloid with a central 2,5-diketopiperazine (DKP) ring. The key step in our synthetic route is a copper-catalyzed sequential arylation–alkylation of o-haloanilide derivatives. Based on this transformation, the construction of C3 all-carbon quaternary stereocenters presented in the HPI systems was achieved with high yields and excellent diastereoselectivity.

Bioinspired Brønsted Acid-Promoted Regioselective Tryptophan Isoprenylations

“…Subsequent total syntheses and accompanying spectroscopic analyses led to the revision of the stereochemical assignment to its cyclo - d -Trp- d -Trp core. Although the 1 H and 13 C spectra arising out of independent synthetic endeavors were in a full agreement with the natural product isolated by Capon et al , the optical rotation studies of the synthetic compound led to the reassignment of stereochemistry . As shown in Figure B, a nOe signal of 2.62% between C2–H and C3–Me indicated a cis relative stereochemistry at the B–C ring fusion (C2C3).…”

Copper(I)‐Catalyzed Cascade Cyclization to the Total Synthesis of Hexahydropyrroloindole Alkaloids: Flustramine B and Debromoflustramine B

“…For alcohols 10, which was synthesized from aniline 11 and γbutyrolactone 12 by an ammonolysis and alkylation process, and then oxidized to aldehyde and condensed with S-tertbutylsulfonamide to give imine 9 (Scheme 2). [25][26][27][28] Initially, we commenced our investigations starting from the commercially available 2,5-dibromoaniline 11 and γbutyrolactone 12 which underwent an ammonolysis and alkylation process in the presence of trimethylaluminum (AlMe 3 ), providing alcohol derivative 13 with 95 % yield. Nisopentenylation of the alcohol 13 offered the compound 10 in 94 % yield under a basic condition, which was then oxidized by Dess-Martin periodinane (DMP) to give the corresponding aldehyde 14 with 91 % yield.…”

“…For the past decades, many novel synthetic routes have been reported for the construction of these architectures, and to further access hexahydropyrroloindole (HPI) alkaloids, [13][14][15][16][17][18][19][20][21] such as MacMillan, Trost, Zhang, You and Zhao et al To our knowledge, most routes often relied on substituted indoles or tryptophan derivatives as starting materials, however, only a few reports were based on non-indole or nonoxindole. [15,[22][23][24] To address these limitations, Zhang group [25][26][27][28][29] has developed a novel copper(I)-catalyzed tandem reaction strategy to achieve several natural products of hexahydropyrroloindole alkaloids, such as (À )-Debromoflustramine E, (+)-Chimonanthine, (À )-Ditryptophenaline and (+)-Nocardioazine B et al Based on previous work, to continue our interest in studying the total synthesis of Hexahydropyrroloindole (HPI) alkaloids, herein we report a complementary route for the total synthesis of Flustramine B and Debromoflustramine B via a cascade cyclization process starting from non-indole or non-oxindole catalyzed by Copper (I).…”

Biosynthesis of pyrroloindoline-containing natural products

“…To date, several elegant total synthesis works have been reported, but all suffer from long steps and low yield. [133][134][135] In 2015, Norah et al analyzed the genome of Nocardiopsis sp. CMB-M0232 and identied the noz cluster, which includes a cyclodipeptide synthase (NozA), a prenyltransferase (NozC), a methyltransferase (NozB), and two cytochrome P450s (NozD and NozE).…”