Total synthesis of myxol and deoxymyxol stereoisomers and their application to determining the absolute configurations of the natural products

The total synthesis of myxol stereoisomers 1a,b and deoxymyxol (plectaniaxanthin) stereoisomers 2a,b was accomplished by Wittig reaction of (S)- and (R)-C₁₀-phosphonium salts 8a,b bearing a silyl-protected 1,2-dihydroxy-ψ end group with C₃₀-apocarotenals 6 and 7. The phosphonium salts 8a,b were derived from aldehydes 11a,b possessing a cyclopentylidene ketal moiety, prepared via Sharpless asymmetric epoxidation of allylic alcohol 12 followed by regioselective cleavage of the oxirane ring. We established an analytical HPLC method using a chiral column to separate stereoisomers 1a,b and 2a,b and thus determined the absolute configurations of the natural products. The HPLC analyses established that both myxol and deoxymyxol isolated from bacteria have the 2′S-configuration.     

5,6-二亚甲基二环[2.2.1]庚-2-醇的四种立体异构体的合成与构型

本文报道了手性桥环化合物5,6-二亚甲基二环[2.2.1]庚-2-醇的四种光学纯立体异构体的合成及其比旋光度[α]~D, 并通过它们之间的相互关系, 确定了它们的绝对构型.     

Determination of the conformations and relative configurations of exocyclic amines

The conformations and relative configurations of 20 amines, classified according to the following labeling scheme, were analyzed. Series a comprised compounds derived from N-(1-phenylethyl)cyclohexanamine, b comprised derivatives of N-[1-(naphthalen-2-yl)ethyl]cyclohexanamine, c comprised derivatives of N-(diphenylmethyl)cyclohexanamine, and d comprised derivatives of N-(propan-2-yl)cyclohexanamine. The compounds were labeled as follows: 1 indicates cyclohexanamine, 2 indicates 2-methylcyclohexanamines, 3 indicates 3-methylcyclohexanamines, 4 indicates 4-methylcyclohexanamines, and 5 indicates 4-tert-butylcyclohexanamines. These compounds were prepared without the use of stereoselective induction and, therefore, all expected stereoisomers were observed. Structural assignments were established by (1)H, (13)C, and (15)N NMR.     

Determination of ephedrine alkaloid stereoisomers in dietary supplements by capillary electrophoresis

Three complementary capillary electrophoresis (CE) methods were developed for the separation and quantification of ephedrine and pseudoephedrine stereoisomers. Either single or dual cyclodextrin-based chiral selector systems provided enantioselective separation of the compounds of interest. The three methods were applied to the analysis of a suite of five standard reference materials (SRMs) containing ephedra. Use of a high-sensitivity UV detection cell enhanced quantification of the analytes of interest over the wide range of concentrations encountered in the SRMs. Results for (-)-ephedrine ranged from 0.31 to 76.43 mg/g, and for (+)-pseudoephedrine ranged from 0.049 to 9.23 mg/g in the materials studied. Results from the three methods agreed well with each other and with the results from other methods of analysis. The addition of known amounts of specific enantiomers was used to confirm the enantiomeric identity of the analytes. The results obtained by the three CE methods were utilized for value assignment of the ephedrine alkaloid content of these five SRMs.     

Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers

[reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13.     

Synthesis of four stereoisomers of protected 1,2-epiimino-3-hydroxypropylphosphonates

Enantiomerically pure protected 1,2-epiimino-3-hydroxypropylphosphonates were synthesised from hydroxy-1-{[(R)- or (S)-1-phenylethyl]aziridin-2-yl}methylphosphonates via regioselective ring opening with acetic acid followed by a stereospecific intramolecular cyclisation of 3-acetoxy-1-mesyloxy-2-(1-phenylethyl)aminopropylphosphonates and hydrogenolytic removal of the 1-phenylethyl group in the presence of Boc₂O. The trans-isomers of 3-acetoxy-[N-(1-phenylethyl)-1,2-epiimino]propylphosphonates exist as a 2:1 mixture of invertomers, which were fully structurally characterised based on their ¹H and ¹³C NMR spectroscopic data. Large differences in the ¹J_C-P values in N-(1-phenylethyl)aziridine-2-phosphonates were noticed depending on the spatial arrangement of the nitrogen lone pair and the phosphorus atom (syn-periplanar—ca. 215 Hz; anti-periplanar—182 Hz).     

Total syntheses of four possible stereoisomers of resolvin E3

Resolvin E3, 17,18-dihydroxy-5Z,8Z,11Z,13E,15E-eicosapentaenoic acid, is a potent anti-inflammatory lipid mediator. To determine the stereochemistries of the C17- and C18-hydroxy groups of resolvin E3 and to supply a sufficient amount of material for future biological studies, we developed a highly convergent and practical route to its four possible stereoisomers. The key reactions employed here were the Horner–Wadsworth–Emmons coupling, the two copper(I)-mediated reactions between the alkynes and the propargyl tosylates, and the simultaneous reduction of the three triple bonds to the three Z-olefins.     

Determination of threo and erythro configurations of 3-fluorophenylalanine for verifying stereochemical aspects of recently reported syntheses

Determination of threo and erythro configurations of both diastereoisomers of 3-fluorophenylalanine on the basis of chemical transformation and X-ray analysis has confirmed that the aziridine ring opening reaction gives the threo isomer stereoselectively, whereas the fluorodehydroxylation reaction affords both isomers nonselectively.     

Determination of one-centre core integrals from the average energies of atomic configurations

One-center core integrals for valence orbitals are determined from the experimental average energies of neutral atomic configurations from Li through Zn. These values are compared with those estimated from CNDO /1, “INDO /1”, CNDO /2, “INDO /2” and with theoretical values calculated from a pseudo-potential method. The agreement is good between values obtained from neutral atoms and from the psuedo-potential calculation except for the 3d orbitals of the transition elements where the theoretically calculated integrals over single ξ functions are not realistic. These two methods reproduce both term and average configuration energies for the first two rows of atoms; the semiempirical method reliably reproduces them for the third row. The CNDO /1 and INDO /1 methods underestimate atomic energies, while the CNDO /2 and INDO /2 procedures fail rather poorly. The propriety of using core integrals estimated semiempirically in molecular orbital calculations is discussed.     

NMR Determination of absolute configurations in 2-alkylthiazolidine-4-carboxylic acids

The condensation of L-cysteine with enantiomerically pure aldehyde 2a and 2b afforded a mixture of 2- substituted thiazolidine diastereomers 1a-b and 1c-d , respectively. The present paper deals with the use of nuclear Overhauser effect (nOe) in determining the absolute configurations of the stereocenters.     

Determination of cis and trans configurations in pentahydrobenzopyranopyrroles by FT-IR spectroscopy

A method of distinguishing cis and trans isomers in polyheterocycles containing β,β′-disubstituted pyrrolidines is described. It is based on the relative absorbance of the Bohlmann bands and the normal symmetric CH stretching bands. The method is applied using FT-IR spectroscopy in solution and coupled with gas chromatography. An interpretation is given, with the help of molecular computing.     

Theoretical study of the stereoisomers of tetrahydrocannabinols

A theoretical AM1 semiempirical study of the major active components of marijuana and their stereoisomers is presented. It was found that the calculated partition coefficients, dipole moments, heats of formation, volume, surface area, ovality, and conformation of the pyran ring cannot explain the activity differences between the stereoisomers. The major factor is the orientation of the carbocyclic ring and its C₁ substituent with respect to the phenyl group hydroxyl oxygen. Our study has revealed and supports the involvement of previously described steric features of cannabinoids in determining their biological potency. Based on these conclusions, we predicted the relative activities for the (+)-cis-δ¹-THC, (-)-cis-δ¹-THC, (+)-cis-δ⁶-THC, and (-)-cis-δ⁶-THC stereoisomers, which have not been synthesized. © 1997 John Wiley & Sons, Inc.     

Two stereoisomers of the rat toxicant norbormide

The structures of two diastereoisomers of norbormide {systematic name: 5‐[hydroxy­(phenyl)(2‐pyridyl)­methyl]‐8‐[phenyl(2‐pyridyl)­methyl­ene]‐3a,4,7,7a‐tetra­hydro‐4,7‐methano‐1H‐iso­indole‐1,3(2H)‐dione}, viz. the unsolvated mol­ecule, C₃₃H₂₅N₃O₃, and the ethyl acetate hemisolvate, C₃₃H₂₅N₃O₃·0.5C₄H₈O₂, have been determined unambiguously. They differ in the relative stereochemistry about the exocyclic double bond and the relative conformations of the aryl rings. Each compound exhibits both intra‐ and intermolecular hydrogen bonding.     

Asymmetric synthesis of all the stereoisomers of tarchonanthuslactone

We describe herein an efficient synthesis of all the four stereoisomers of tarchonanthuslactone from (R)-3-hydroxy butanoate, easily prepared from l-threonine. The approach involves the use of a β,γ-unsaturated δ-lactone as an intermediate, obtained via a Kulinkovich reaction followed by a ring-closing metathesis strategy.     

Mass spectra of dihydroxy stereoisomers of 3-methoxy-1,3,5(10)-estratrienes

Electron impact mass spectral data for each of the four isomeric 16,17-, 15,17- and 14,17-diols of 3-methoxy-1,3,5(10)-estratriene and the 15,17-diols of 3-methoxy-14β-1,3,5(10)-estratriene are reported. The mass spectra of the diols show very similar fragmentation patterns except for differences in the relative abundances of particular ions. The different [M ? H₂O]⁺˙/[M] ⁺˙ and [M ? 2H₂O] ⁺˙ [M] ⁺˙ ratios can be used for distinguishing between the four isomeric 3-methoxy-1,3,5(10)-estratriene-14,17-diols as well as between the four isomeric 3-methoxy-14β-1,3,5(10)-estratriene-15,17-diols. No significant differences could be detected in the spectra of the epimeric 16,17-and 15,17-diols of 3-methoxy-1,3,5(10)-estratriene.     

Enantiopure synthesis of all four stereoisomers of carbapenam-3-carboxylic acid methyl ester

The retro-Dieckmann reaction has been used as a stereodivergent synthetic tool on N-Boc-7-azabicyclo[2.2.1]heptan-2-one-1-carboxylic acid methyl ester to obtain enantiopure trans- and cis-5-(carboxymethyl)pyrrolidine-2-carboxylic acid methyl esters. These disubstituted pyrrolidines have been used as starting materials to develop concise and straightforward syntheses of all four stereoisomers of carbapenam-3-carboxylic acid methyl esters. In this way, we have confirmed unequivocally the stereochemistry of two carbapenams isolated from strains of Serratia and Erwinia species.