Mollenynes B–E from the Marine Sponge Spirastrella mollis. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

Abstract

Four new chlorobromohydrins, mollenynes B-E, were isolated from the marine sponge Spirastrella mollis collected from Hogsty Reef, Bahamas. Their structures were elucidated by integrated analysis of NMR, MS, and computational methods. A high-resolution band-selective HSQC experiment was developed to identify (13)C NMR signals in samples at the nanomole-scale that arise from Cl-substituted (13)C by exploiting the (35)Cl/(37)Cl isotope shift.

Evaluation of Band-Selective HSQC and HMBC: Methodological Validation on the Cyclosporin Cyclic Peptide and Application for Poly(3-hydroxyalkanoate)s Stereoregularity Determination

“…Aliasing of signals resonating outside of the chosen selectivity zone is obviously a problem for both quantification applications (in case an aliased signal would be superimposed with a studied signal) and structural studies where bs-HSQC is used for improving 13 C resolution. This problem does not seem to have been reported by previous authors using this selectivity method [31][32][33][34].…”

“…Improved spectral resolution found applications in structure elucidation of compounds exhibiting crowded spectral regions, such as peptides [23,24,26] or oligosaccharides [25,[27][28][29][30]. More recently, bs-HSQC has been used for studying 35,37 Cl isotope shift for 13 C [31][32][33][34] and for quantifying purposes; its improved sensitivity (compared to direct 13 C Polymers 2018, 10, 533 3 of 14 acquisition) allows studying the relative abundance of triad signals in polyacrylonitrile samples [22] or even isotopomers signals in halogenated natural products [33]. 13 C selectivity was first obtained using "soft pulses": soft 90 • or 180 • 1 H pulses (low power rectangular pulses), manipulating only Hα in peptides and observing C(=O) [23,24], or soft 180 • 13 C pulse (DANTE pulse train) in the first INEPT step of HSQC, transferring magnetization only to the desired 13 C [25].…”

“…Pulsed Field Gradient Spin-Echoes (PFGSE) were first introduced for solvent signal suppression [36,37] and were used in bs-heteronuclear experiments, either for direct 13 C selectivity in HSQC or HMBC experiments [26,29], or for elimination of unwanted peptide protecting group resonances (DPFGSE applied on the 1 H region of protecting groups) [38]. Recently, band-selectivity in HSQC-related experiments was obtained using highly selective shaped pulses (Gaussian cascade [39,40]) for 13 C refocalization during the reverse-INEPT step in place of the adiabatic pulses used for uniform broadband refocalization [31][32][33][34], or using them in a DPFGSE inserted in the HSQC sequence [22]. Herein, we describe an evaluation of bs-HSQC and HMBC experiments as quantitative tools.…”

Marine natural products

“…The biosynthesis of these compounds could involve an unusual "dyotropic shi" of Cl and Br atoms, which would also account for the observed inversion of congurations within the series. 600 The known fungal metabolites gibepyrones C 868 and F 869 (ref. 601) were isolated from the marine environment for the rst time.…”

Ultra‐high resolution band‐selective HSQC for nanomole‐scale identification of chlorine‐substituted 13C in natural products drug discovery

“…Here, and in every other case discussed in this report, Figure 1. Mollenynes A (1) [6] and B (2), [7] synthetic bromochloroalkanes 3 and 4, and polyhalogenated terpenes (5-7) from Plocamium cartilagineum. Cl-related signal because of the slightly greater spin-orbit effect and shorter C-Cl bond length for the heavier isotope.…”