Assignment of the C5' relative stereochemistry in (+)-lepadin F and (+)-lepadin G and absolute configuration of (+)-lepadin G.
ABSTRACT: Concise assignments of the C5' stereochemistry in (+)-lepadin F and (+)-lepadin G and the absolute configuration of (+)-lepadin G via the first total syntheses of (+)-5'-epi-lepadin F, (+)-lepadin G, and (+)-5'-epi-lepadin G are described. This work represents an illustrative example in which a diastereomeric pair can possess sufficient spectroscopic difference for clear assignment despite differing only at a highly insulated acyclic stereocenter.
Project description:Radicinin and cochliotoxin (1 and 2) two phytotoxic pyranpyran-4,5-diones were isolated together with their close metabolites 3-epi-radicinin, radicinol, and its 3-epimer (3-5), from the culture filtrates of Cochliobolus australiensis, a fungus proposed as mycoherbcide for biocontrol of buffelgrass, a very noxious and dangerous weed. The absolute configuration of cochliotoxin was determined by chiroptical Optical Rotatory Dispersion (ORD), Electronic Circular Dichroism (ECD), and Vibrational Circular Dichroism (VCD)) and computational methods. The same methods were used to confirm that of radicinin, radicinol and their 3-epimers, previously determined with chemical, spectroscopic and ECD methods.
Project description:The plants of the genus Kadsura are widely distributed in China, South Korea, and Japan. Their roots and stems are traditionally used to treat blood diseases and pain. The main bioactive constituents of Kadsura longipedunculata comprise highly oxygenated triterpenoids. Schiartane-type nortriterpenoids showed anti-HIV, anti-HBV, and cytotoxic bioactivities. For such compounds, the absolute configuration influences the bioactivities, and hence its unambiguous determination is essential. In this work, the absolute configurations of three highly oxygenated schiartane-type nortriterpenoids were unequivocally assigned using X-ray, ECD, and J-based configuration analysis and HSQC overlay data.The ethanol extract of Kadsura longipedunculata Finet et Gagnep was purified by column chromatography using silica, Sephadex LH-20, and ODS as substrates. To help assign the absolute configuration of schiartane-type nortriterpenoids, X-ray diffraction analysis, ECD experiment compared to ab initio computed data, DP4+ analysis, HSQC overlay, NOESY, and J-based configuration analysis were carried out. Hetero- and homo-nuclear coupling constants were extracted from HETLOC experiments.Three new highly oxygenated triterpenoids, micrandilactone I (1), micrandilactone J (2), and 22,23-di-epi-micrandilactone J (3) were isolated. Their 2D structures were solved using NMR and HRESIMS data and their absolute configurations were elucidated using X-ray diffraction analysis, ECD experimental results compared to ab initio computed spectra, HSQC overlay, DP4+, NOESY, and J-based configuration analysis. Micrandilactone I (1) and 22,23-di-epi-micrandilactone J (3) showed moderate hepatoprotective activity against APAP-induced toxicity in HepG2 cells with cell survival rates of 53.0 and 50.2%, respectively, at 10?M (bicyclol, 49.0%), while micrandilactone J (2) was inactive.This is the first comprehensive stereochemical assignment of a non-crystalline schiartane-type nortriterpenoid like 3. This general protocol may contribute towards solving the problems hampering the assignment of the absolute configurations of other members of this class of nortriterpenoids.
Project description:A highly stereoselective synthesis of 11-acetoxy-4-deoxyasbestinin D (1) has been completed in 26 linear steps. The synthesis hinges on a selective glycolate aldol addition to establish the C-2 stereocenter, a ring-closing metathesis reaction to complete the oxonene, and an intramolecular Diels-Alder cycloaddition to establish the relative configuration at C-1, C-10, and C-14. This initial total synthesis of an asbestinin also serves to confirm the absolute configuration of this subclass of the C-2-C-11-cyclized cembranoid natural products.
Project description:The synthesis and absolute configuration of SCH 351448, an interesting ionophoric natural product, are reported herein. Mukaiyama aldol-Prins and segment-coupling Prins reactions were employed to construct the constituent tetrahydropyrans of SCH 351448. Efforts to assemble the C2-symmetric core of the natural product by a templated olefin metathesis strategy are described; however, a stepwise fragment assembly was ultimately utilized to complete the target molecule.
Project description:The structurally complex oligomeric proanthocyanidins (OPACs) are promising biomimetic agents, capable of strengthening the macromolecular backbone of teeth via intermolecular and intermicrofibrillar cross-linking. This study establishes analytical methods capable of determining the absolute configuration of the catechin-type monomeric units of underivatized OPACs. This preserves the capacity of their biological evaluation, aimed at understanding the inevitably stereospecific interactions between the OPACs and dentin collagen. Guided by dental bioassays (modulus of elasticity, long-term stability), two new trimeric and tetrameric A-type OPACs were discovered as dentin biomodifiers from pine (Pinus massoniana) bark: epicatechin-(2??O?7,4??8)-epicatechin-(2??O?7,4??8)-catechin (5) and epicatechin-(2??O?7,4??8)-epicatechin-(2??O?7,4??6)-epicatechin-(2??O?7,4??8)-catechin (6), respectively. Combining 1D/2D NMR, HRESIMS, ECD, 1H iterative full spin analysis (HiFSA), and gauge-invariant atomic orbital (GIAO) ? calculations, we demonstrate how 13C NMR chemical shifts (diastereomeric building blocks (A-type dimers)) empower the determination of the absolute configuration of monomeric units in the higher oligomers 5 and 6. Collectively, NMR with ECD reference data elevates the level of structural information achievable for these structurally demanding molecules when degradation analysis is to be avoided. Considering their numerous and deceptively subtle, but 3D impactful, structural variations, this advances the probing of OPAC chemical spaces for species that bind selectively to collagenous and potentially other biologically important biomacromolecules.
Project description:The absolute configuration of gymnocin-B has been determined to be (S)-10 and (S)-37. Three challenges toward the configurational assignment of this largest of the polyether marine toxin include (i) introduction of p-(meso-triphenylporphyrin)-cinnamate group (TPPcinnamate) on sterically hindered 10-, 37-hydroxyls under mild conditions, (ii) conformational analysis in the presence of TPPcinnamates at C-10 and C-37 positions on the flexible seven-membered rings embodied in a large polyether ladder-like scaffold structure, and (iii) determination of the chirality at C-10 and C-37 on the basis of porphyrin/porphyrin circular dichroism exciton-coupled interaction over a large distance. The experimentally obtained positive exciton couplet by CD and FDCD of the bis-TPPcin derivative of gymnocin-B is in good agreement with that of theoretically calculated CD of the MMFF optimized structures, by employing DeVoe's coupled oscillator approach, thus establishing the full absolute configuration of gymnocin-B.
Project description:A Kiyooka aldol condensation of an aldehyde with a trimethylsilyl ketene acetal and the oxazaborolidinone prepared from N-Ts-(S)-valine gives two of the four possible aldol adducts, which were oxidized and deprotected to complete the synthesis of (-)-berkelic acid and (-)-22-epi-berkelic acid. This synthesis establishes the absolute stereochemistry and assigns the stereochemistry at C-22. A biosynthetic pathway is proposed that is consistent with the known absolute stereochemistry at the quaternary carbon of spiciferone A, spicifernin, and berkelic acid and provides a simple explanation for the differing stereochemistry at C-18 and C-19 of spicifernin and berkelic acid.
Project description:The first enantioselective synthesis of (+)-isolysergol was completed in 12 steps from commercially available materials by a novel approach that features a late stage microwave-mediated, diastereomeric ring-closing metathesis catalyzed by a chiral molybdenum catalyst to simultaneously form the D ring and set the stereocenter at C(8).
Project description:The absolute stereostructure of sagittamide A (1), a O-hexacetyl long-chain hexahydroxy-alpha,omega-dicarboxylic acid, was assigned using a progressive-convergent approach that integrates three powerful regimens for stereochemical analysis of acyclic natural products: J-based analysis, 13C NMR universal database comparisons, and exciton coupling circular dichroism.
Project description:Scoring permutations of experimental chemical shift deviations and DFT/GIAO calculated deviations of isotropic shieldings for sets of four diastereomers can help to assign their relative configurations. This method was exercised on a set of diastereomeric Cinchona alkaloid derivatives, where 13C NMR data always identified the proper configuration. The presented approach is also an attempt to quantify the assignment by exclusion.