Assignment Of Absolute Stereochemistry Research Articles

L-Galactose as a natural product: isolation from a marine octocoral of the first α- l-galactosyl saponin

Saponine 1 (6′- O-acetyl-3β-pregna-5,20-dienyl-α- l-galactopyranoside), that contains a l-galactose moiety linked to the aglycone through an infrequent α-glycosidic bond, has been isolated from the marine octocoral Muricea c.f. purpurea. This constitutes the first report on the occurrence of l-Gal as a nonpolymeric natural product. A CD procedure for the absolute stereochemical assignment of saponins, based on the CD analysis of its perbenzoylated derivative, is proposed.

Assignment of Absolute Stereochemistry and Total Synthesis of (−)-Spongidepsin

Assignment of Absolute Stereochemistry and Total Synthesis of (−)-Spongidepsin

Assignment of absolute stereochemistry and total synthesis of (-)-spongidepsin.

[structure: see text] An enantioselective total synthesis of (-)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis.

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1 , ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.

2-(2,3-Dihydro-1H-indol-3-yl)ethanol: synthesis, separation of enantiomers, and assignment of absolute stereochemistry by X-ray structure analysis.

The first direct resolution of racemic 2-(2,3-dihydro-lH-indol-3-yl)ethanol-prepared by catalytic hydrogenation of 2-(lH-indol-3-yl)ethanol-has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single-crystal X-ray analyses were successful, revealing that the (+)-enantiomer of 2-(2,3-dihydro-lH-indol-3-yl)ethanol has the (S) configuration. Chirality 16:126-130, 2004.

Convergent Enantioselective Synthesis of Vinigrol, an Architecturally Novel Diterpenoid with Potent Platelet Aggregation Inhibitory and Antihypertensive Properties. 1. Application of Anionic Sigmatropy to Construction of the Octalin Substructure

The coupling of building blocks 15 and 36e in the presence of MgBr(2).OEt(2) at 0 degrees C proceeds with an exo stereoselectivity (3.2:1) considerably more advantageous for the acquisition of carbinol 37e than in the absence of the additive (exo/endo = 1:5.7). The pivotal transformation that sets all of the relevant stereocenters of the cis-octalin 55 is the oxyanionic-accelerated [3,3]-sigmatropic rearrangement of 37e. A salient feature is the structurally enforced adoption of a boatlike transition state that serves to properly set four vicinal methine hydrogens in an all-cis arrangement. The ensuing conversion of 55 into iodo sulfone 62 has permitted X-ray crystallographic confirmation of all absolute stereochemical assignments since the isopropyl substituent was initially installed enantioselectively via the Evans oxazolidinone protocol. No intramolecular anionic cyclization of 62 to generate the tricyclic framework was seen. This absence of reactivity is attributed to conformational factors that inhibit attainment of the proper S(N)2 reaction trajectory.

Enantioselective synthesis of (-)-terpestacin and (-)-fusaproliferin: clarification of optical rotational measurements and absolute configurational assignments establishes a homochiral structural series.

An enantioselective synthesis of the syncytium formation inhibitor (-)-terpestacin (1, 19 steps, 5.8% yield from the allylation product of (R,R)-pseudoephedrine propionamide, 3) and the fungal metabolite (-)-fusaproliferin (2, 21 steps, 5.3% yield from 3) in their natural configurations is described. The route employs a series of stereoselective enolate alkylation reactions to establish the initial stereogenic center, set the quaternary carbon configuration, close the 15-membered ring, and introduce the side-chain residue with proper stereocontrol. Careful analysis of our synthetic materials alongside natural samples has revealed that several errors were made in the earlier measurements of optical rotation or in the absolute stereochemical assignments of these natural products. Clarifying all discrepancies, we show here that natural terpestacin (1) is levorotatory, not dextrorotatory as originally described, but was correctly assigned as the (1S,11S,15R,23S)-enantiomer. Fusaproliferin (2) is levorotatory, as reported, but is in fact the (1S,11S,15R,23S)-enantiomer and not the antipodal configuration originally assigned.

Total synthesis of the mycolactones.

[structure: see text] The first total synthesis of the mycolactones is reported. This work unambiguously confirms our earlier relative and absolute stereochemical assignment of the mycolactones.

Structure revision and assignment of absolute stereochemistry of a marine C21 bisfuranoterpene.

The C21 bisfuranoterpene (-)-isotetradehydrofurospongin-1 (6), previously isolated from a Western Australian Spongia sp., has been reisolated from a specimen of Spirastrella papilosa collected during scientific trawling operations in the Great Australian Bight. A 2D NMR analysis of 6 has prompted reassignment of the published structure 5, while degradation and chiral HPLC analysis have allowed determination of the absolute stereochemistry.

ChemInform Abstract: Synthesis and Absolute Stereochemistry Assignment of Enantiopure Dihydrofuro‐ and Dihydropyrano‐quinoline Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and characterization of homochiral cholesteryl 1-alkenesulfinate esters

A number of α,β-unsaturated sulfinyl chlorides 1 has been separately prepared and treated with (−)-cholesterol under various conditions some of which incorporated chiral amines quinine or quinidine. Some (RS) vinylic sulfinates could be isolated in enantiopure form following one or two recrystallizations of the resulting diastereomeric mixtures of (−)-cholesteryl 1-alkenesulfinates 2. Access to diastereomerically enriched (SS) vinylic sulfinates (66–75% de) was achieved in three instances. Absolute stereochemical assignments were made with the assistance of the chiral solvating agent (R)-2,2,2-trifluoro-1-(9-anthryl)ethanol.

Structure Determination and MS n Analysis of Two New Lissoclinamides Isolated from the Indo–Pacific Ascidian Lissoclinum patella: NOE Restrained Molecular Dynamics Confirms the Absolute Stereochemistry Derived by Degradative Methods

Two new lissoclinamides, lissoclinamides 9 and 10 were isolated from an Indonesian collection of the ascidian Lissoclinum patella along with the known patellamide C. The structures of the lissoclinamides were determined by a combination of 2D NMR, selective 1D TOCSY, MS and MS n techniques. The assignment of absolute stereochemistry was achieved by the hydrolysis of lissoclinamides 9 and 10 followed by chiral TLC. In the case of lissoclinamide 9, NOE restrained molecular dynamics studies were also performed confirming the proposed stereochemistry.

Synthesis of harzialactone A and its isomers from d-glucose and assignment of absolute stereochemistry

The synthesis of the marine metabolite (3 R,5 R)-harzialactone A 1 from d-glucose is described. Syntheses of all the isomers (3 S,5 R)- 2, (3 R,5 S)- 3 and (3 S,5 S)- 4 of 1 are also described and the absolute stereochemistry for the natural product 1 is assigned unambiguously.

First enantioselective total synthesis of (natural) (+)-11,12-epoxy-11,12-dihydrocembrene-C and (−)-7,8-epoxy-7,8-dihydrocembrene-C

The first enantioselective total syntheses of (+)-11,12-epoxy-11,12-dihydrocembrene-C 1 and (−)-7,8-epoxy-7,8-dihydrocembrene-C 2, two naturally occurring cembranoxides isolated from tropical marine soft corals, are achieved via a general approach by employing an intramolecular McMurry coupling and Sharpless asymmetric epoxidation as key steps from readily available starting materials. The syntheses presented here verify the absolute stereochemistry assignment of 1 as (11S,12S) by Bowden et al. two decades ago, and the epoxy configuration of 2 was assumed as (7R,8R) accordingly.

Synthesis and absolute stereochemistry assignment of enantiopure dihydrofuro- and dihydropyrano-quinoline alkaloids

The chiral quinoline alkaloids platydesmine 3, platydesmine methosalt 4 and edulinine 9, have been synthesised in enantiopure form via asymmetric dihydroxylation of the achiral alkaloid atanine 1. Chromatographic separation of MTPA diastereoisomers 20 formed from racemic bromohydrin derivatives of atanine 1 was a key step in the synthesis of geibalansine 7, edulinine 9, ribalinine 10, Ψ-ribalinine 11 and araliopsine 12 as single enantiomers. The absolute configurations of (+)-platydesmine methosalt 4 and (−)-Ψ-ribalinine 11 were unequivocally determined by X-ray crystallography while stereochemical correlation and circular dichroism spectroscopy methods were used to assign absolute configurations to platydesmine 3, geibalansine 7, ribalinine 10, araliopsine 12 and edulinine 9. Possible errors which earlier led to the incorrect assignment of absolute configurations of the quinoline alkaloids platydesmine 3, platydesmine methosalt 4, edulinine 9, araliopsine 12 and other related chiral quinoline alkaloids are discussed.

Synthesis and Absolute Stereochemical Assignment of (+)-Miyakolide

The first total synthesis of the marine macrolide miyakolide has been achieved, and its absolute stereochemistry has been determined. The carbon skeleton is assembled in a convergent fashion from t...

Synthesis, biological activity, and absolute stereochemical assignment of NPS 1392: a potent and stereoselective NMDA receptor antagonist

The synthesis, biological activity, and single crystal X-ray structure of NPS 1392, ( R)-(−)-3,3-bis(3-fluorophenyl)-2-methylpropan-1-amine ( 3a), a potent, stereoselective antagonist of the NMDA receptor, are described. The NMDA receptor selectively bound the levo isomer ( 3a) over its enantiomer ( 3b), which prompted a rigorous absolute configuration assignment. NPS 1392 has the R configuration based on the single-crystal X-ray diffraction analysis of the hydroiodide salt of NPS 1392. This compound is a potential neuroprotective agent for use in the treatment of ischemic stroke.

Resolution of polycyclic aromatic hydrocarbon dihydrodiols via diastereomeric formaldehyde acetals

Diastereomeric formaldehyde acetals, formed from the reaction of racemic benzo[ a]pyrene dihydrodiol and (−)-chloromethylmenthyl ether, are novel intermediates for effecting the convenient resolution of these metabolites by HPLC. This resolution technique seems generally applicable since the dihydrodiols of benzo[ c]phenanthrene can also be readily resolved through this methodology. Key differences in the proton NMR spectra of the diastereomeric dihydrodiol menthyloxymethyl ethers have been identified which could be used for absolute stereochemical assignments.

Aldol reactions of ketal-protected tartrate ester enolates. Asymmetric syntheses and absolute stereochemical assignments of phospholipase A 2 inhibitors cinatrin C 1 and C 3

An efficient approach to the syntheses of cinatrins C 1 and C 3 has been developed and used to establish the absolute configurations of these natural products. The construction of each molecule has been achieved in a five-step reaction sequence (overall yield 43% for cinatrin C 1, 33% for cinatrin C 3) from the di- tert-butyl ester of ( R, R)-tartaric acid. The two contiguous, quaternary chiral centers in the cinatrin skeleton are constructed via a diastereoselective, titanium-mediated aldol coupling of a tartrate-derived silylketene acetal and an achiral α-ketoester. This bond construction proceeds with excellent diastereoselectivity for a variety of aldehyde and α-ketoester substrates.

Enantioselective Synthesis of the Elaiophylin Aglycon.

Elaiophylin (1) was isolated in 1959 by Arcamone and co-workers from cultures of Streptomyces melanosporus.1 Subsequently, this natural product has also been obtained from other strains of Streptomyces.2 Structure elucidation of 1, including assignment of absolute stereochemistry, was based on chemical degradation,3 NMR studies,4 and ultimately X-ray crystallographic analysis.5 Isolation and characterization of the elaiophylin aglycon, elaiolide (2), was accomplished by Zeeck and Bindseil in 1993 through deglycosylation of 1.6