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Antheridiol-(22,23-3H) has been prepared by reduction of 3-acetoxy-23,23-dihydroxy-22-oxo-5, 24(28)-ergostadiene-28-carboxylic acid gamma - lactone with tritiated sodium borohydride followed by hydrolysis, photo-oxygenation and cupric chloride catalysed rearrangement.

A versatile synthetic route to pterosins, sesquiterpenoid indanones present in bracken, Pteridiumaquilinum, has been developed. The route is exemplified by the synthesis of (2S,3S)-pterosin C by Friedel–Crafts bisacylation of the methyl ether of 2-(2,6-dimethylphenyl)ethanol with methylmalonyl chloride. Demethylation of the resulting 1,3-indandione and reduction with zinc and acetic acid in the presence of acetic anhydride and sodium acetate afforded a mixture of racemic cis and trans isomers of pterosin C diacetate, which was hydrolysed to the corresponding pterosins. Separation and resolution via the S-(+)-α-phenylbutyric esters gave (2S,3S)-pterosin C and (2R,3R)-pterosin C. Other pterosins were prepared as racemates from the 1,3-indandione.

Cholesterol beta-D-glucoside-6'-O-palmitate has been identified as a polar metabolite in the mycelium of mated cultures of Pythium sylvaticum grown in the presence of cholesterol. The structure was confirmed by synthesis of the metabolite. Similar steroid beta-D-glucoside-6'-O-palmitates were obtained from beta-sitosterol and campesterol when these sterols were added to cultures of P-sylvaticum. Corresponding esters of myristic and stearic acids were also detected.

Fucosterol-[3- 3 H] was converted to the oogoniols, sex hormones of Achlya , in A. heterosexualis . A similar conversion occurred in A. ambisexualis provided antheridiol was added.

3β-Acetoxyandrost-5-en-17-one has been converted into 15β-hydroxy-24-oxocholesterol. Reaction of (17E)-3β-(dimethyl-t-butylsilyloxy)-15β,16β-epoxypregna-5,17(20)-diene with the magnesium cyanocuprate derivative of 3-(1,3-dioxolan-2-yl)-4-methylpentyl bromide gave (20R)-3β-(dimethylt-butylsilyloxy)-15β-hydroxy-24-oxocholesta-5,16-diene 24-ethylene acetal in 80% yield, and this was converted into the target compound in high yield by catalytic hydrogenation followed by removal of the protecting groups. Reaction of 3β,15β-diacetoxycholest-5-en-24-one with the anion of diethyl cyanomethylphosphonate and reduction of the resulting nitrite with DIBAL-H, gave 15β,29-dihydroxyfucosterol. This was converted into the 3,29-diacetate 15-formate and oxidized with chromium trioxide–3,5-dimethylpyrazole. Removal of the acetate and formate groups with aqueous potassium carbonate afforded 15β,29-dihydroxy-7-oxofucosterol.

3β,11α,15β-Trihydroxy-5-pregnen-20-one, an intermediate required for the synthesis of the oogoniols, has been prepared from 15α-hydroxy-11-oxo-progesterone in an overall yield of 16%. The three isomers (at C-11, C-15) of the pregnene were also prepared.

An X-ray crystallographic analysis of illudin S, an anitumor sesquiterpene from Omphalotusilludens, has been carried out. Crystal data: C15H20O4, orthorhombic, space group P21212, a = 15.103(5), b = 10.574(5), c = 8.917(3) A, Z = 4, F(000) = 568, λ (Cu) = 1.54184 A. Final residual index R = 0.037. Interatomic distances indicate nonbonded repulsive interactions between the methylenes of the cyclopropane ring and the adjacent tertiary hydroxyl and methyl groups. Relief of this interaction may explain the ready isomerization of illudins to isoilludins. Molecular mechanics calculations show isoilludin M to be ∼5 kcal/mol more stable than illudin M in agreement with this postulate. Reaction of illudin M with dilute HCl gives two chloroindantriols by nucleophilic attack of chloride on the cyclopropane ring leading to a quinoid intermediate which is trapped by solvent. mudins can thus act as bifunctional alkylating agents.

The synthesis of tritiated male-activating steroids of the aquatic fungus Achlya, 7-deoxy-7-dihydroantheridiol (7-DA) and antheridiol, has been achieved by aldol condensation of 3β-acetoxy-23,24-dinorchola-1,5-dien-22-al and the carbanion of 3-isopropyl-2-butenolide. The product with the desired stereochemistry (22S,23R) was isolated and reduced with 3H2 in the presence of tris(triphenylphosphine)rhodium chloride. Acid hydrolysis of the acetate gave 1,2[3H]-7DA which had a specific activity of 40 Ci/mmol. 1,2[3H]-7DA was converted to 1,2[3H]-antheridiol by protecting the hydroxyl groups as the disilyl ethers, oxidation to the 7-ketone with chromium trioxide-dimethylpyrazole and removal of the protecting groups by gentle acid treatment. 1,2[3H]-7DA has been used to detect a protein receptor in the cytosol of Achlya.

Sexual reproduction among the eukaryotic fungi of the genus, Achlya, is controlled by two steroid pheromones. Antheridiol is the pheromone constitutively produced by female cells that induces male sexual differentiation and development. A biologically active tritium-labeled derivative of antheridiol, [1,2-3H]7-deoxy-7-dihydro-antheridiol ( [3H]7dA), has been synthesized. Radioligand-binding studies have revealed the presence of a specific binding protein in the cytosol of male cells that may represent the endogenous receptor for antheridiol. Binding to this macromolecule was characterized by an apparent equilibrium dissociation constant and maximum binding capacity of approx. 7 X 10(-10) M and 1 100-2 000 fmoles/mg protein, respectively. Sedimentation analysis in sucrose gradients revealed that the binding protein distributes in the 8S region under low ionic strength and sodium molybdate-stabilized conditions. Under conditions of high ionic strength, in the presence or absence of 10 mM sodium molybdate, the binding site distributes in the 3.6S region of the gradient. Analysis of radioligand binding in the presence of other steroids and steroid hormones revealed that the binding is specific for antheridiol and its analog.

Synthese du compose du titre a partir de la progesterone. La premiere etape est une hydroxylation microbiologique. La chaine laterale est ensuite construite par reaction de Wittig

When grown in the presence of [CD3]-methionine Achlya heterosexual produces oogoniols containing two deuterium atoms which are located at C-28

In feeding experiments withAchlya heterosexualis, [3-(3)H] fucosterol was efficiently incorporated into oogoniols possessing an unsaturated side chain as well as those with a saturated side chain (clionasterol skeleton). [23,25-(3)H]-29-Hydroxyfucosterol was also efficiently incorporated into the oogoniols and its role as an intermediate in the biosynthesis was confirmed by a trapping experiment. This indicated the presence of a small pool of endogenous 29-hydroxyfucosterol in the mycelium. [23, 25-(3)H]-29-Oxofucosterol was also well incorporated into the oogoniols and it is probably an intermediate in the biosynthesis. It was found to be converted to 29-hydroxyfucosterol in a trapping experiment. Reduction of the C-24(28) double bond make take place after all the functional groups have been introduced, at C7, C-11 and C-15, in the tetracyclic structure.

On decrit une synthese stereoselective du brassinolide. La chaine laterale est construite par reaction du methoxy-6β cyclo-3,5 pregnane-5α carbaldehyde-20 avec l'anion du dimethyl-2,3 butenolide

The structure of dehydro-oogoniol (3 beta,11 alpha,15 beta,29-tetrahydroxystigmasta-5,24(28)(E)-dien-7-one), a female-activating hormone of the water mold Achlya, has been confirmed by synthesis. The starting material was progesterone, which was converted to the 11 alpha, 15 beta-dihydroxy derivative by microbiological hydroxylation with Aspergillus giganteus (ATCC 10059). The side chain was constructed in a stepwise manner by means of Wittig and Horner-Emmons reactions, and the C-7 ketone was then introduced by allylic oxidation. The biological activity of the synthetic compound was the same as that of the natural hormone.

Fungi in the order Saprolegniales are known to contain varying proportions of sterols, such as cholesterol and fucosterol. In the caseAchyla, it has been found that fucosterol, the major sterol component, serves as the biosynthetic precursor of the hormones, antheriodiol and the oogoniols. Antheridiol is secreted by female strains ofAchlya and induces the formation of antheridial hyphae in male strains. It also causes the male to secrete the oogoniols which induce the formation of oogonial initials in female strains. Antheriodiol is responsible for the chemotropic growth of the antheridial hyphae to a developing oogonium which results in sexual conjugation. The structures, biosynthesis, and functions of these hormones are discussed in this paper.

3β-Acetoxyandrost-5-en-17-one has been converted into 15β-hydroxy-24-oxocholesterol. Reaction of (17E)-3β-(dimethyl-t-butylsilyloxy)-15β,16β-epoxypregna-5,17(20)-diene with the magnesium cyanocuprate derivative of 3-(1,3-dioxolan-2-yl)-4-methylpentyl bromide gave (20R)-3β-(dimethylt-butylsilyloxy)-15β-hydroxy-24-oxocholesta-5,16-diene 24-ethylene acetal in 80% yield, and this was converted into the target compound in high yield by catalytic hydrogenation followed by removal of the protecting groups. Reaction of 3β,15β-diacetoxycholest-5-en-24-one with the anion of diethyl cyanomethylphosphonate and reduction of the resulting nitrite with DIBAL-H, gave 15β,29-dihydroxyfucosterol. This was converted into the 3,29-diacetate 15-formate and oxidized with chromium trioxide–3,5-dimethylpyrazole. Removal of the acetate and formate groups with aqueous potassium carbonate afforded 15β,29-dihydroxy-7-oxofucosterol.

We have tested derivatives of progesterone obtained by fermentation with Aspergillus giganteus for relative binding affinity for the progesterone receptor of chick oviduct. Our studies show that hydroxyl and oxo substitutents at C-11 and C-15 of progesterone significantly decrease the hormone's affinity for the progesterone receptor. The loss in affinity on introduction of a C-15 hydroxyl in 17-hydroxyprogesterone is restored by acetylation to 15β-acetoxy-17 hydroxyprogesterone. The latter compound may have some potential as an in vivo agent.

The fungal metabolite lepiochlorin has been synthesized from allylmethoxyethoxymethyl ether and the dianion of 2-phenylthiopropionic acid. The resulting lactone was converted to the butenolide and halogen functions introduced by hydrolysis of the MEM group and treatment with thionyl chloride followed by N-bromosuccinimide. Reaction with silver acetate yielded lepiochlorin.