Stereoselectivity of directed epoxidations of 22-hydroxy-Δ23-sterol side chains

1996 ◽  
Vol 74 (10) ◽  
pp. 1857-1867 ◽  
Author(s):  
Thomas G. Back ◽  
Denise L. Baron
Keyword(s):  
Molecular Modeling ◽  
Parent Compound ◽  
Allylic Alcohol ◽  
Allylic Alcohols ◽  
Methyl Groups ◽  
Side Chains ◽  
Molybdenum Hexacarbonyl ◽  
Reliable Prediction ◽  
Tert Butyl Hydroperoxide ◽  
Threo Isomer

A series of 22-hydroxy-Δ23-sterols comprising (3β,5α,6β,22S)-6-methoxy-3,5-cyclo-25,26,27-trinorcholest-23-en-22-ol (6), (3β,5α,6β,22S,23E)-6-methoxy-3,5-cyclo-26,27-dinorcholest-23-en-22-ol (7), 3β,5α,6β,22R)-6-methoxy-23-methyl-3,5-cyclo-25,26,27-trinorcholest-23-en-22-ol(10),3β,5α,6β,22S,23Z)-6-methoxy-3,5-cyclo-26,27-dinorcholest-23-en-22-ol (11), and 3β,5α,6β,22R)-6-methoxy-3,5-cyclo-26,27-dinorergost-23-en-22-ol (12) were subjected to epoxidation with m-chloroperbenzoic acid and tert-butyl hydroperoxide in the presence of either vanadyl acetoacetonate or molybdenum hexacarbonyl, and the threo:erythro ratios of the products were determined. The results are of relevance for the synthesis of sterols with oxygenated side chains, such as brassinolide (1). The oxidations of 6 and 7 were erythro selective with all three oxidants, especially with the vanadium-catalyzed system. Peracid oxidation of the 22-tert-butyldimethylsilyl ether (8) and 22-pivaloate (9) of alcohol 7 showed similar erythro selectivity to that of the parent compound 7. Allylic alcohol 10 gave exclusively the erythro epoxide with all three oxidants, while 11 and 12 were threo-selective under all three conditions. Molecular modeling indicated that erythro selectivity in the vanadium-catalyzed epoxidation of 10 was consistent with a destabilizing interaction (A(1,2) strain) between the gem-methyl and C(21) methyl groups in the conformation required for formation of the threo-isomer. The threo-selective peracid oxidations of 11 and 12 were attributed to A(1,3) strain between the cis-methyl groups and C(20) in the conformation required for formation of the erythro-epoxide. The differences in the calculated energies of conformations leading to the threo- and erythro epoxide diastereomers of substrates containing no gem or cis substituents proved too small to permit reliable prediction of diastereoselectivity. Key words: 22-hydroxy-Δ23-sterols, brassinosteroids, allylic alcohols, epoxidation, diastereoselectivity

Cyanoalkylation/alkynylation of allylic alcohol through intramolecular radical 1,2-alkynyl migration

2021 ◽  
Vol 19 (11) ◽  
pp. 2416-2419
Author(s):  
Shengnan Jin ◽  
Fan Chen ◽  
Pengcheng Qian ◽  
Jiang Cheng
Keyword(s):  
Allylic Alcohol ◽  
Allylic Alcohols ◽  
Butyl Peroxide

A di-tert-butyl peroxide (DTBP)-promoted difunctionalization of α-aryl α-alkynyl allylic alcohols with alkyl nitriles was developed, affording a series of α-alkynyl γ-cyano functionalized ketones in moderate yields.

SYNTHESIS OF DERIVATIVES OF 1,2-DICHLORO-4-BENZENESULFONAMIDO-5-NITROBENZENE AND THEIR USE IN THE CHEMOTHERAPY OF SPONTANEOUS CANCERS

1965 ◽  
Vol 43 (5) ◽  
pp. 1454-1459 ◽  
Author(s):  
D. W. Woolley ◽  
T. Van Der Hoeven
Keyword(s):  
Active Substance ◽  
Quaternary Ammonium ◽  
Water Solubility ◽  
Parent Compound ◽  
Para Position ◽  
Methyl Groups ◽  
Chlorine Atoms ◽  
Derivatives Of ◽  
Ionizable Groups

A series of compounds related to 1,2-dichloro-4-benzenesulfonamido-5-nitrobenzene has been synthesized. These included derivatives in which ionizable groups had been placed in the para position of the benzenesulfonamido portion to confer on the compounds water solubility at physiological pH. Thus, carboxyl and quaternary ammonium groupings were introduced in this position. Water solubility was also conferred by introduction at the same position of non-ionizable groups such as polyhydroxyalkylamido groups. Additional relatives of the parent compound in which the chlorine atoms were replaced by methyl groups, and in which para-substituted benzenesulfonamido groups replaced those in the 4 and 5 positions, were synthesized. These compounds were tested for their ability to cure permanently the spontaneous mammary cancers of two strains of mice. All compounds were tested in combination with 1,2-dimethyl-4-(p-carboxyphenylazo)-5-hydroxybenzene. The most active substance found was 1,2-dichloro-4-(p-carboxybenzenesulfonamido)-5-nitrobenzene.

The Structure of Elastomers and Their Reactivity

1951 ◽  
Vol 24 (1) ◽  
pp. 95-98
Author(s):  
A. S. Kuz'minskii ◽  
N. N. Lezhnev
Keyword(s):  
Molecular Weight ◽  
Methyl Groups ◽  
Side Chains ◽  
Double Bonds ◽  
Gutta Percha ◽  
Different Temperatures ◽  
Spatial Configurations ◽  
The Mean ◽  
Kinetics Of ◽  
Mean Molecular Weight

Abstract It has not yet been ascertained what constituent parts within the structure of various elastomers have the greatest influence on the reactivity of the elastomers. There are indications that the side chains, the presence of methyl groups acting as substitutes, and differences in spatial configurations, etc., all have definite effects. The present authors have investigated the oxidation of several different elastomers at different temperatures. The experiments were carried out both in the presence and in the absence of an inhibitor (phenyl-β-naphthylamine). The elastomers and the inhibitor were first carefully purified. The kinetics of autoxidations were studied volumetrically by means of an apparatus already described by one of the authors. A chainless molecular introduction of oxygen into the double bonds of the elastomer in the presence of the inhibitor was studied with the aid of our own previously described inhibitor methods. The study included the oxidation of butadiene elastomers containing different distributions of double bonds in the main and side chains, divinylstyrene rubber, and the hydrocarbons of natural rubber and gutta-percha. These products are distinguished by their different degrees of unsaturation, the number of side chains, the number of double bonds in both their main and side chains, the length of their molecular chains (the mean molecular weight), and their spatial configurations.

Sharpless Asymmetric Epoxidation: Applications in the Synthesis of Bioactive Natural Products

2020 ◽  
Vol 17 ◽  
Author(s):  
Suélen Karine Sartori ◽  
Izabel Luzia Miranda ◽  
Marisa Alves Nogueira Diaz ◽  
Gaspar Diaz-Muñoz
Keyword(s):  
Natural Products ◽  
Building Blocks ◽  
Heterocyclic Ring ◽  
Biologically Active ◽  
Asymmetric Epoxidation ◽  
Allylic Alcohols ◽  
Titanium Tetraisopropoxide ◽  
Bioactive Natural Products ◽  
Tert Butyl Hydroperoxide ◽  
Sharpless Asymmetric Epoxidation

: This review discusses an important synthetic tool proposed by K. B. Sharpless in 1980, known as the Sharpless asymmetric epoxidation of allylic alcohols, and examines its use in the total synthesis of representative exponents of biologically active natural products. Focus is given to the synthesis of simple to highly complex secondary metabolites, including lactones, amino acids, diterpenes, and macrolides. The Sharpless approach involves the use of a catalyst, titanium tetraisopropoxide [Ti(OiPr)4], dialkyl tartrate as chiral ligand, and tert-butyl hydroperoxide (TBHP) as oxidizing agent. The method allows converting allylic alcohols to epoxides, which are chiral building blocks and versatile intermediates in the synthesis of natural products. The biological and synthetic importance of epoxides lies in the susceptibility of the threemembered heterocyclic ring to stereo- and regioselective opening by nucleophilic or acidic reagents, providing oxygen adducts.

The Nakada Synthesis of (-)-FR182877

2013 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Complex Mixture ◽  
Alder Reaction ◽  
Single Step ◽  
Diels Alder ◽  
Allylic Alcohol ◽  
Allylic Alcohols ◽  
Weinreb Amide ◽  
Diels Alder Reaction ◽  
Reaction Matrix ◽  
Stereogenic Centers

The Streptomyces metabolite (-)-FR182877 3 binds to and stabilizes microtubules, showing the same potency of anticancer activity as Taxol (paclitaxel). Masahisa Nakada of Waseda University assembled (Angew. Chem. Int. Ed. 2009, 48, 2580) the hexacyclic ring system of 3 by the tandem intramolecular Diels-Alder–intramolecular hetero Diels-Alder cyclization of 1, generating seven new stereogenic centers in a single step. The construction of the pentaene substrate 1 started with the known aldehyde 4, prepared by homologation of commercial ethyl 3-methyl-4-oxocrotonate. Addition of the propionyl oxazolidine anion 5 proceeded with high diastereocontrol, to give 6. The acyl oxazolidinone was not an efficient acylating agent, so it was converted to the Weinreb amide. Protection and deprotection then delivered the allylic acetate 7. The key step in the pentaene assembly was the carefully optimized Negishi-Wipf methylation of 8, followed by Pd-mediated coupling of the alkenyl organometallic so generated with the allylic acetate, to give 9. Condensation of the derived keto phosphonate 11 with the known aldehyde 12 then delivered the enone 13. The Nakada group has worked extensively on the intramolecular Diels-Alder reaction of substrates such as 1. They have shown that protected anti diols such as 1 cyclize with substantial diastereocontrol and in the desired sense. In contrast, cyclizations of protected syn diols proceed with poor diastereocontrol. The enone 13 was therefore reduced to the anti diol and protected, leading to 14 . Oxidation of 14 at room temperature led to a complex mixture, but slow oxidation at elevated temperature delivered 2 . Although the yield of 2 was not much better than if the reactions were carried out sequentially, first the intramolecular Diels-Alder cyclization, then the intramolecular hetero Diels-Alder cyclization, with the cascade protocol pure 2 was more readily separated from the reaction matrix. With 2 in hand, there was still the challenge of assembling the seven-membered ring. Cyclization was effected with an intramolecular Heck protocol. The two diastereomers of the allylic alcohol 15 cyclized with comparable efficiency. Ir-catalyzed alkene migration then converted the allylic alcohols to a mixture of ketones, which was equilibrated to give the more stable diasteromer.

Hydride Reductions of 1-Phenyl-1-nonen-3 -one: Mass Spectrometry of 1-Phenyl-1-nonen-3-ols and Relative Stereochemistry of the Diastereoisomeric 4-Dimethylaminomethyl-1-Phenyl-1-nonen-3-ols

1974 ◽  
Vol 52 (13) ◽  
pp. 2522-2530 ◽  
Author(s):  
Wesley Gordon Taylor ◽  
Jonathan Richard Dimmock
Keyword(s):  
Aluminum Hydride ◽  
Addition Product ◽  
Mannich Bases ◽  
Allylic Alcohol ◽  
Lithium Aluminum ◽  
Allylic Alcohols ◽  
Carbonyl Carbon Atom ◽  
Methyl Radical ◽  
Mass Spectral ◽  
Relative Stereochemistry

The metal hydride reduction products of some styryl ketones and dimethylaminomethyl Mannich bases have been investigated. Sodium borohydride selectively attacked the carbonyl carbon atom to give the desired allylic alcohols. Reduction of 1-phenyl-1-nonen-3-one with lithium aluminum hydride gave 1-phenyl-3-nonanol which represents the conjugate addition product. Fragmentations of 1-phenyl-1-nonen-3-ol were compared to the modes of mass spectral breakdown of 4-phenyl-3-buten-2-ol, an allylic alcohol which is known to behave like a saturated ketone on electron bombardment. Peaks corresponding to the McLafferty ion and the loss of a methyl radical from this rearrangement product were observed. Certain Mannich bases were reduced to diastereoisomeric allylic amino alcohols. The separation, 1H n.m.r. spectroscopy, and relative stereochemistry of the diastereoisomers are discussed.

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