Total synthesis of Phytophthora mating hormone α1

Total synthesis of Phytophthora mating hormone α1 (1) has been demonstrated. The required stereochemistries (methyl) are achieved by applying CuI-(S)-Tol-BINAP-catalyzed conjugate addition of Grignard reagents to α,β-unsaturated esters.     

Synthesis and spectroscopic analysis of a stereoisomer library of the phytophthora mating hormone α1 and derived bis-Mosher esters

Fluorous mixture synthesis provided all eight diastereomers of the phytophthora hormone α1 with the R configuration at C11 as individual samples after demixing and detagging. The library of all possible bis-Mosher esters (16) was then made by esterification. Complete sets of (1)H, (13)C, and (for the Mosher esters) (19)F NMR spectra were recorded, assigned, and compared with each other and with published spectra. Not all of the spectra are unique, and the (1)H NMR spectra of the Mosher esters provided the most information. The previous assignment of the natural sample as an "all-R" stereoisomer mixed with its 3S-epimer was confirmed.     

Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30 μM, IC50=1.40 μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.     

Total synthesis of the α-subunit of human glycoprotein hormones: toward fully synthetic homogeneous human follicle-stimulating hormone

Described herein is the first total chemical synthesis of the unique α-subunit of the human glycoprotein hormone (α-hGPH). Unlike the biologically derived glycoprotein hormones, which are isolated as highly complex mixtures of glycoforms, α-hGPH obtained by chemical synthesis contains discrete homogeneous glycoforms. Two such systems have been prepared. One contains the disaccharide chitobiose at the natural N-glycosylation sites. The other contains dodecamer oligosaccharides at these same sites. The dodecamer sugar is a consensus sequence incorporating the key features associated with human glycoproteins.     

Synthesis of New α-Heterocyclic α-Aminophosphonates

α-heterocyclic α-aminophosphonates were obtained in good yields by N-of several nitrogen heterocycles with α-azido-α-aminophosphonate 1. ¹ Elachqar, A., El Hallaoui, A., Roumestant, M. L. and Viallefont, Ph. 1994. Synthetic Comm, 24: 1279 [CSA][Taylor & Francis Online], [Web of Science ®] , [Google Scholar]     

New general synthesis of α-alkoxyketones via α'-alkylation, α-alkylation and α,α'-dialkylation of α-alkoxyketimines

α-Methoxy- and α-ethoxyketones, as important intermediates in organic synthesis and flavor compounds in food chemistry, were synthesized by deprotonation of N-(1-alkoxy-2-propylidene)isopropylamine, prepared by condensation of the corresponding α-alkoxyacetone with isopropylamine, and subsequent reaction of the corresponding 1-azaallylic anions with alkyl halides to afford α'-alkylated, α-alkylated and α,α'-dialkylated ketimines. Hydrolysis of the imino function led to the desired substituted α-alkoxyketones. The ratio of α-, α'-, and α,α'-(di)alkylated compounds depended on the amount of base used and on the nature of the alkylating reagent.     

Convenient synthesis of α-diarylmethylphosphonates by HOTf catalyzed Friedel-Crafts arylation of α-aryl α-hydroxyphosphonates

We report a convenient catalytic Friedel-Crafts arylation of α-aryl α-hydroxyphosphonates with various (hetero)aromatic compounds. HOTf (trifluoromethanesulfonic acid) is identified to be the best Brønsted acid catalyst, and the desired α-diarylmethylphosphonates were obtained in up to 41–95% yield.     

Synthesis of α-Telluroketones

α-Telluroketones were prepared by reacting 4-methoxyphenyltellurium trichloride either with ketones or silyl enol ethers of ketones. The products upon pirolysis furnish α-chloro ketones.     

Addition of some α-halogeno ethers to α-thiooxides of alkenes

Summary Products of the addition of allyl chloromethyl ether, -chloroethyl methyl ether, -acetoxyethyl chloromethyl ether, cyclohexyl chloromethyl ether, and -chloroethyl ethyl ether to the thiooxides of ethylene and propylene have been prepared.     

Preparation of α-Halovinyl Sulfides by Eliminative Deoxygenation of α-Halosulfoxides

Abstract

Vinyl sulfides are useful synthetic intermediates¹ which have received increasing attention recently both as masked carbonyl moieties² and in carbon-carbon bond forming reactions.³ With regard to the latter, vinyl sulfide derivatives which are substituted in the α-position with halogen, tin, selenium, etc., are particularly useful due to the ready formation of anions upon treatment with a variety of organometallic reagents.^{3 d ? 1} We report here that synthetically useful halovinyl sulfides can be produced in high yield by the eliminative deoxygenation of the corresponding α-halosulfoxides induced by electrophilic silicon reagents.     

Synthesis of α-alkylthioacroleins

Monomeric -alkylthioacroleins were obtained by the reaction of alkylthioacetaldehydes with formaldehyde and diethylamine hydrochloride. The structures of the -alkylthioacroleins were confirmed by NMR spectroscopy and mass spectrometry as well as by chemical transformations of these compounds.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 188–190, January, 1996.     

Carbonylation of α-Haloketones

The catalytic carbonylation reactions of -haloketones in the presence of palladium compounds were studied. Chloroketones were selectively converted into -ketoesters, whereas bromoacetophenone was partially reduced to acetophenone. The reaction rate at atmospheric pressure was much lower than that at an elevated pressure. A reaction mechanism was proposed.     

Study of the enantioselectivity of the CAL-B-catalysed transesterification of α-substituted α-propylmethanols and α-substituted benzyl alcohols

A study of the enantioselectivity exhibited by the lipase B from Candida antarctica in the transesterification of different α-substituted α-propylmethanols with vinyl acetate is shown. The best results are obtained when the large-sized (L) substituent of the alcohol is either a phenyl group or more especially a cyclohexyl group, although the reaction rates are lower than when linear or slightly branched groups are present. It is also found that ramification at the β-position of the L substituent has a deleterious effect on both lipase activity and enantioselectivity. Moreover, some α-substituted benzyl alcohols bearing medium-sized (M) substituents larger than an ethyl and smaller than a propyl group are resolved by means of this methodology with moderate-good enantioselectivities (E=46–57) and similar reaction rates.     

Synthesis of α-oxazolinylalkanamides

The synthesis of α-oxazolinylalkanamides 2, based on the reaction of α-chloroalkyloxazolines 1 with hexacarbonyltungsten [W(CO)₆] and lithium amides, has been developed. A plausible mechanism involving the ketene 5 as the intermediate is also proposed.     

Preparation of n-oxides of α− and α′-A minonicotines

Summary All possible N-oxides of -benzamidonicotine were prepared and were hydrolyzed with hydrochloric acid to N-oxides of the corresponding -aminonicotines.     

Synthesis of α-hydroxyacetophenones

A general method for the preparation of α-hydroxyacetophenones is presented. Functionalized arylmagnesium species are transmetalated to the corresponding arylzinc intermediates, which undergo Cu(I)-catalyzed reaction with acetoxyacetyl chloride. Acidic hydrolysis of the acetate group releases the target α-hydroxyacetophenones with minimal production of undesired polymeric degradates that are often observed under alternative conditions.     

Organocatalytic synthesis of α-hydroxy and α-aminophosphonates

A new and highly flexible procedure is described for the synthesis of α-amino- and α-hydroxy phosphonates. In the presence of a catalytic amount of oxalic acid (10 mol %), trimethyl phosphite reacts with aldehydes or imines (generated in situ from an aldehyde and an amine) to yield the corresponding coupled products in good yield.     

Synthesis of new α-hydroxyphosphonates and α-acetoxyphosphonates

A series of new α-hydroxyphosphonate (5–14) have been synthesized in high yields by reaction of β-chloro-α,β-unsaturated aldehydes (1–4) and trialkyl phosphite in the presence of chlorotrimethylsilane at room temperature under solvent-free conditions. In addition, compounds (5–14) were reacted with acetic anhydride in DBU to give the new α-acetoxyphosphonate derivatives (15–23). All these phosphonates (5–23) were obtained as mixtures of two (E and Z) isomers and fully characterized by multinuclear (¹H, ¹³C, and ³¹P) NMR, IR spectroscopy and HRMS.     

Claisen rearrangement of allylic α-isocyano-esters—regioselective allylation of α-isocyanoesters at the α-carbon

A regioselective allylation of α-isocyanoesters at the α-carbon was achieved by the Claisen rearrangement of allylic α-isocyanoesters via the corresponding silyl ketene acetals in situ generated.