Synthesis and absolute configuration of (1S,8S)-as-hydrindacene-1,8-diol as determined by the circular dichroism exciton chirality method

2,3,6,7-Tetrahydro-as-indacene-1,8-dione 4 was prepared in 4 steps starting from 2-methyl-furan by modification of a literature procedure. Appliance of Noyori’s asymmetric transfer hydrogenation, resulted in (1S,8S)-1,2,3,6,7,8-hexahydro-as-indacene-1,8-diol 5 in high yield (81%) and excellent enantioselectivity (>99% ee) or (8S)-8-hydroxy-3,6,7,8-tetrahydro-2H-as-indacen-1-one 6 in moderate yield (58%) and equally high enantioselectivity (98.5% ee), depending on the conditions. The asymmetric reduction was expected to yield the (S)-alcohols using the (S,S)-Ts-DPEN ligand, which was confirmed by the appliance of the exciton chirality method on the corresponding bis(p-dimethylamino)benzoate 7.     

Stereoselective synthesis of (Z)-axino- and (Z)-debromoaxinohydantoin

(Z)-Axinohydantoin and (Z)-debromoaxinohydantoin, two pyrrole-imidazole alkaloids isolated from different marine sponges, possess moderate activities in inhibiting the progress of the cell cycle at different phases. A stereoselective synthesis of both natural products was achieved. The key step in the synthetic pathway was the installation of the hydantoin northern ring by using 1-benzoyl-2-methylsulfanyl-1,5-dihydroimidazol-4-one.     

Absolute configurations of endoperoxides determined by vibrational circular dichroism (VCD)

Diastereomeric mixture on the peroxide portion of an endoperoxide acetylmajapolene A (1) was efficiently separated by HPLC on a chiral column, submitting to vibrational circular dichroism (VCD) investigation. The ab initio theoretical VCD and IR calculations of 1a and 1b were performed by density functional theory (DFT) using the B3PW91/6-31G(d,p) level of theory. Focusing on an isolated characteristic peroxide vibrational band, absolute configurations of 1a and 1b were unambiguously determined as (1R,4R,7S,10S) and (1S,4S,7S,10S), respectively. This is the first VCD application to endoperoxides which exist abundantly in nature.     

Absolute configuration of scopadulane diterpenes from Calceolaria species

The absolute configuration of the diterpenoid 13-acetoxyscopadulane, also known as demalonyl thyrsiflorin A acetate (5), isolated from several Calceolaria species has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations, as well as by evaluation of Flack and Hooft single crystal X-ray parameters. It follows 5 belongs to the normal enantiomeric series of diterpenes, and that at least 11 out of 13 scopadulanes, for which chemical and biogenetical relationships with 5 are established, also belong to the same stereochemical series.     

Further monoterpene chromane esters from Peperomia obtusifolia: VCD determination of the absolute configuration of a new diastereomeric mixture

A reinvestigation of the monoterpene chromane ester enriched fraction from Peperomia obtusifolia using chiral chromatography led to the identification of a minor peak, which was elucidated by NMR and HRMS as fenchyl-3,4-dihydro-5-hydroxy-2,7-dimethyl-8-(3″-methyl-2″-butenyl)-2-(4′-methyl-1′,3′-pentadienyl)-2H-1-benzopyran-6-carboxylate, the same structure assigned to two other fenchyl esters described previously, pointing out a stereoisomeric relationship among them. Further NMR analysis revealed that it was actually a mixture of two compounds, whose absolute configurations were determined by VCD measurements. Although, almost no vibrational transitions could be assigned to the chiral chromane, the experimental VCD spectrum was largely opposite to that obtained for the average experimental VCD [(2S,1?R,2?R,4?S + 2R,1?R,2?R,4?S)/2] for fenchol derivatives. These results allowed us to assign the putative compounds as a racemic mixture of the chiral chromane esterified with the monoterpene (1S,2S,4R)-fenchol, which had not been identified in our early work.     

Deconvolution of E/Z tetrahydroisoquinoline amide rotamers and conformers from a marine-derived Streptomyces strain

A collaborative program to discover new specialized metabolites from aquatic environments of Iceland led to the deconvolution of tetrahydroisoquinoline amide E/Z rotamers [(E/Z)-N-acetyl-MY336-a; 1] and conformers produced by a Streptomyces sp. All structures were elucidated by NMR and MS analysis, and interpretation of electronic circular dichroism (ECD) data. ECD and optical rotation (OR) simulations permitted the unequivocal assignment of the absolute configuration of compound 1 and provided an important example of delineating the spectroscopic contributions of equilibrating rotamers and boat/chair conformers of a common natural product scaffold.     

Total syntheses of the highly potent anti-cancer polyacetylenes, (S)-18-hydroxyminquartynoic acid, (S)-minquartynoic acid and (E)-15,16-dihydrominquartynoic acid

The total syntheses of three polyacetylenic natural products, (S)-18-hydroxyminquartynoic acid (1), (S)-minquartynoic acid (2) and (E)-15,16-dihydrominquartynoic acid (3), has been achieved. The Cadiot-Chodkiewicz cross-coupling reaction was used as the key step for the construction of tetrayne and triyne units.     

Application of the Cosford cross-coupling protocol for the stereoselective synthesis of (R)-(+)-goniothalamin, (R)-(+)-kavain and (S)-(+)-7,8-dihydrokavain

An efficient and versatile synthetic method has been developed and utilized for the stereoselective synthesis of (R)-(+)-goniothalamin 1, (R)-(+)-kavain 2 and (S)-(+)-7,8-dihydrokavain 3. Application of the Cosford protocol and direct conversion of aldehydes to β-keto-esters are the key steps in our approach.     

Caldorin,a new polyketide from the marine cyanobacterium Caldora penicillata

A new polyketide with a cis-fused decalin ring scaffold, caldorin, was isolated from the marine cyanobacterium Caldora penicillata. The gross structure and relative configuration were elucidated by spectroscopic analyses. We also clarified that caldorin is a weak SOAT inhibitor and moderate osteoblast differentiation inhibitor. On the other hand, caldorin did not exhibit cytotoxicity against either HeLa or HL60 cells.     

Introduction of a planar chirality onto steroid substrates: synthesis of (S) and (R)-2′-formylcymantrenyl-17α-ethynylestradiols using (S) and (R)-1-formyl-2-iodo-cymantrenes

We report the synthesis and characterisation of (S) and (R)-2′-formylcymantrenyl-17α-ethynylestradiol synthesized using the Sonogashira cross-coupling reaction between optically pure (S) and (R) 1-formyl-2-iodo cymantrenes and ethynylestradiol. (S) and (R) 1-formyl-2-iodo cymantrenes were obtained from the same precursor: (2R,4R)-4-(methoxymethyl)-2-cymantrenyl-1,3-dioxane.     

Synthesis to determine the absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea

The absolute configuration of (−)-pyricuol, a phytotoxin isolated from rice blast disease fungus Magnaporthe grisea, was determined to be R by synthetic studies.     

Synthesis of Bis(indole) Alkaloids from Arundo donax: The Ynindole Diels–Alder Reaction,Conformational Chirality,and Absolute Stereochemistry

Bis(indole) alkaloids from Arundo donax were synthesized using the first ynindole Diels–Alder reaction. The alkaloids are chiral, having stable enantiomeric conformations with half‐lives of racemization of t_1/2=4150–25100 seconds at room temperature. Their absolute stereochemistry was determined using the exciton chirality method.     

Synthesis and absolute configuration of hylodiglyceride isolated from Hylodendron gabunensis

A recently isolated bismonoglyceride of heptadecanedioic acid, which represents a novel type of natural monoglycerides (i.e., with two instead of only one glycerol unit in the molecular architecture), was synthesized in enantiopure forms using a chiral-pool based approach with the 17-carbon chain constructed from undec-10-enoic acid and oct-7-en-1-ol via a cross metathesis and the stereogenic centers derived from (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanol. An analogue with a longer alkyl chain was also synthesized. The synthetic samples not only allowed for establishment of the absolute configuration but also helped to reveal some minor yet unignorable errors in the ¹H NMR data for the natural product. Optical rotation and NMR data acquired in DMSO and DMSO-d₆, respectively, are also presented.     

Podospermic acid, 1,3,5-tri-O-(7,8-dihydrocaffeoyl)quinic acid from Podospermum laciniatum (Asteraceae)

A phytochemical investigation of Podospermum laciniatum (L.) DC. (Asteraceae) yielded the new quinic acid derivative podospermic acid (1,3,5-tridihydrocaffeoylquinic acid), which was named after the genus it was isolated from. The structure was established by HR mass spectrometry and extensive 1D and 2D NMR spectroscopy. Podospermic acid is the first naturally occurring dihydrocaffeoylquinic acid derivative. The chemosystematic impact and the radical scavenging activity of the new compound are discussed briefly.     

The preparation of ketone constituents from Echinacea pallida

Efficient syntheses of two ketones from Echinacea pallida are described.     

Absolute configuration of bioactive expansolides A and B from Aspergillus fumigatus Fresenius

In addition to antafumicins A and B, and cytochalasin, the bioactive compounds expansolides A and B have been isolated from Aspergillus fumigatus Fresenius. Their absolute configuration has been established by using the modified Mosher's method. The bioactivity of all isolated compounds has been evaluated.     

Ikirydinium A: a new indole alkaloid from the seeds of Hunteria umbellata (K. Schum)

Chemical investigations into samples of Hunteria umbellata (K. Schum) collected in Osun State, Nigeria, led to the discovery of a new indole alkaloid, ikirydinium A, featuring an unprecedented 3-alkylpyridinium-indole-2-carboxylate scaffold. Ikirydinium A was found to exhibit antimicrobial activity (IC₅₀ 0.6 μM) against Bacillus subtilis ATCC 6051. The involvement of a common intermediate in the biosynthesis of ikirydinium A and vinblastine is hypothesized.     

Sesterterpene metabolites from the sponge Hyatella intestinalis

The sponge Hyatella intestinalis from the Gulf of California contains the new scalarane-related sesterterpenes hyatelones A-C and hyatolides A-B, together with the new scalaranes hyatolides C-E, hyatelactam, 12-O-deacetyl-19-epi-scalarin and the new norscalarane 12-O-deacetylnorscalaral B. The structures of the new metabolites have been established by spectroscopic analysis of the natural products and, in some instances, of their acetyl derivatives. The new compounds hyatelone A, 19,20-di-O-acetylhyatelone B, hyatolide A, 20-O-acetylhyatolide C, hyatelactam, and 12-O-deacetylnorscalaral B have shown activity as growth inhibitors of several tumor cell lines.     

(-)-Menthol as a source of new N,N-diamine ligands for asymmetric transfer hydrogenation

The synthesis of new chiral N-monotosylated-1,2-diamines based on the (-)-menthol skeleton is presented. The elimination of HCl from neomenthyl chloride obtained from an Appel reaction led to p-menth-3-ene in excellent yield. Further functionalization of the double bond in p-menth-3-ene with chloramine-T gave the corresponding N-tosylaziridines, which upon reaction with sodium azide and subsequent reduction of the azide functional group, formed the 1,2-diamine system. The synthesized chiral ligands proved effective in the asymmetric transfer hydrogenation of aromatic ketones and an endocyclic imine.