N–N‐Coupled Indolo‐sesquiterpene Atropo‐Diastereomers from a Marine‐Derived Actinomycete

Abstract

Four new indolo‐sesquiterpenes – dixiamycins A (1) and B (2), oxiamycin (3), and chloroxiamycin (4) – were isolated from a marine‐derived Actinomycete and characterized, together with the known compound xiamycin A (5). Dixiamycins A (1) and B (2) are the first examples of atropisomerism of naturally occurring N‐N‐coupled atropo‐diastereomers, with a dimeric indolo‐sesquiterpene skeleton and a stereogenic N‐N axis between sp3‐hybridized nitrogen atoms. Solution TDDFT ECD calculations were utilized to ascertain the axial chirality of 1 and 2, and rotational barriers and transitions states of the inversion were calculated. Oxiamycin (3) contains a seven‐membered 2,3,4,5‐tetrahydrooxepine ring. The two dimeric compounds 1 and 2 showed better antibacterial activities than the monomers 3–5.

A twist of nature – the significance of atropisomers in biological systems

“…During characterisation of metabolites from marine Streptomyces, Zhang et al re-isolated the previously discovered xiamycin A (Figure 11, Compound 33), alongside a series of novel N-C and N-N linked xiamycin dimers, 76 compounds also detected in parallel studies by Hertweck et al [77][78][79] Though atropisomeric N-N axes have been observed between sp 2 -hybridized nitrogen atoms in synthetic studies, 80 this discovery marked the first incidence of a naturally-occurring atropdiastereomeric N-N axis between sp 3 -hybridized carbazole nitrogens. The formulae of two atropdiastereomeric compounds were determined to be C 46 H 48 N 2 O 6 using HR-FAB/MS (highresolution fast atom bombardment), corresponding to a dimer of xiamycin A.…”

“…The rotational energy barriers of 34 and 35 were found to be 199 kJ.mol -1 and 201 kJ.mol -1 respectively, consistent with experimental data showing thermal interconversion of the two could not be achieved even by heating at 100 °C for 1 hour. 76 Figure 10: The known structure of xiamycin A (33), and determined structures of dixiamycin A (34) dixiamycin B (35), and an unnamed C-N linked xiamycin dimer (36), of which both the M and P isomers were isolated.…”

Modular Terpenoid Construction via Catalytic Enantioselective Formation of All-Carbon Quaternary Centers: Total Synthesis of Oridamycin A, Triptoquinones B and C, and Isoiresin

“…This effort has resulted in the total synthesis of oridamycin A, 6,7 triptoquinones B and C, 8,9 and isoiresin 10,11 from a common intermediate (Figure 1). Notably, each natural product is prepared in fewer steps than in any prior approach 7,9,11 and, with the exception of isoiresin, protecting groups are not required.…”

Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification

“…We found that xiamycin ( 3 ), the major IST component of the complex20, is diversified by means of rare flavoenzyme-catalysed modifications to yield the cycloether oxiamycin ( 5 )1823, various N,C - and N,N -fused xiamycin dimers (such as 6a/6b )182223, and sulfonyl-bridged xiamycin dimers (such as 7 )19 (Fig. 1).…”