H. O. Huisman

Vitamin A analogues—V : Synthesis of 9-, 13-, and 9,13- desmethyl homologues of vitamin A

Abstract The syntheses of 9-, 13-, and 9,13-desmethyl-vitamin A are described from the corresponding desmethyl homologues of vitamin A acid methyl esters. The latter were prepared by condensation of trans -β-ionylidene acetaldehyde and trans -5-(2′,6′,6′-trimethylcyclohexene-1′-yl-1′)-pentadiene 2,4-al-1 respectively, with the phosphonates of the appropriate crotonic acid esters. Biological investigations on growth promoting properties have shown that all-trans -13- and all-trans -9,13-desmethyl vitamin A acetate are completely inactive, while all-trans -9-desmethyl vitamin A acetate exhibits an activity of about 4%, when compared with all-trans -vitamin A acetate.

Diels-Alder reaction of furan with some dienophiles

Abstract The reaction of furan and maleic acid was carried out in several solvents. The endo-adduct was isolated and the structure established by its spectral properties and conversion into known compounds. The adducts of furan with fumaric acid, diethyl fumarate and diethyl maleate are reported.

Synthesis of substituted 3-aza-bicyclo[3.3.1]Nonanes

Abstract The synthesis of 3-azabicyclo[3.3.1]nonanes is described via the addition of α-bromomethylacrylate 1 to N-tosylpiperidone enamine 4 and subsequent transformation of these adducts. A brief discussion is given on some mechanistic aspects of the addition. NMR-investigation of the various compounds showed a fair correlation between structure and conformation of the adducts and the observed chemical shifts of C H -COOR and N-C H 2 protons.

Synthesis and some reductions of endo- and exo-3,6-epoxy-Δ4-tetrahydrophthalic anhydride

Abstract The synthesis of endo-3,6-epoxy-Δ4-tetrahydrophthalic anhydride from the endo-adduct of furan and maleic acid is described. Reduction of endo- and exo-3,6-epoxy-Δ4-tetrahydrophthalic anhydride with sodium borohydride gave the corresponding lactones, while catalytic hydrogenation over 10% Pd/C gave anhydride and/or hemi-acylals, depending on the solvent.

Dihydroquinolones—V : Hindered inversion in dihydroquinolones and related systems☆

Abstract The NMR spectra of a number of benz[h]dihydroquinolones have been measured. The observed anomalies are explained in terms of a hindered nitrogen inversion. The nature of the phenomenon was demonstrated by appropriate temperature scannings of the spectra and their comparison with the spectra of suitably chosen quinoline derivatives. In the spectrum of a β-disubstituted benz[h]dihydroquinolone the transition of an AB to an A 2 type system was shown to possess an activation energy of 23·0 ± 1·0 kcal/mol.

Chlorination of α-sulfonyl carbanions with hexachloroethane: A novel preparation of α-halosulfones

Abstract The cyclic sulfones 1 , 2 , and 3 are lithiated in benzene with n-butyllithium. Lithiation is demonstrated to lead to α-mono, α,α′-di and/or α,α-di and α,α,α′ trimetallation. The lithiated sulfones are chlorinated with hexachloroethane (HCE). Some mechanistic aspects of the reaction of the lithiosulfones with vicinal dihalides are discussed.

Heterocyclic steroids—III: Mass spectra of 6-azasteroids with two aromatic rings☆

Abstract The mass spectra of the methyl ethers of 6-azaequilenin, 6-aza-14(β)-isoequilenin and their corresponding alcohols have been measured. The postulation of fragmentation pathways and the assignment of structures to the fragments has been based upon the study of suitably labeled deuterium derivatives and recognition of metastable ions. Significant differences in the spectra of stereoisomeric compounds have been related to different modes of decomposition which find their origin in the stereochemistry of the molecules. It is suggested that the mass spectra of these systems may be utilized in diagnosing the stereochemistry of the C/D ring junction.

Heterocyclic steroids. IV. Total synthesis of some 6-aza-estrogens.

Abstract The syntheses of 6-aza-equilenin, 6-aza-estrone and the corresponding C-17 alcohols have been achieved from N-tosyl-6-aza-8, 14-bisdehydroestrone methyl ether (I). Also available via I are the 14β-isomers of the latter estrogens.

The michael induced ramberg-bäcklund homologation to conjugated isoprenoids

Abstract Treatment of the sulfones 1 or 2 with sodium phenylsulfinate in DMSO affords the head-to-tail coupled conjugated monoterpenoids 5–8 in comparable amounts. The corresponding reaction of 3 gives the isomers 16 and 17 . The tail-to-tail homologation of 4 furnishes chiefly a 2 E ,4 E/Z -mixture of the conjugated isoprenoids 18 and 19 . The various isoprenoid mixtures are separated into their components and the configuration of the isomers is established by 1 H NMR double resonance and the NMR/NOE technique. The head-to-tail and tail-to-tail coupled isoprenoid mixtures 5–8 and 18–21 , respectively, are isomerized to 2 E/Z , 4 E -mixtures in a 2:1 ratio. The C 15 -sulfones 11 and 13 are obtained by treatment of 1 with the head-functionalized isoprene synthon 10 . Some speculations on the stereochemical course of the MIRB-homologation are presented.

Vitamin a analogues—III : Determination of the stereochemical configuration of some polyenes of the 4-thia-vitamin a series by NMR spectrometry

Abstract The determination of the stereochemical configuration of several intermediates obtained in the synthesis of 4-thia-vitamin A is described by comparing the NMR spectra of these compounds with those of the carbocyclic analogues of known structure.