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The saponins, conjugated sterols, and free sterols of the sea cucumber Eupentacta fraudatrix were examined. A total of 85 steroids, twelve of them new, were identified in the free sterol, sulfated sterol, and sterol-xyloside fractions. The free sterol fraction contained 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol(6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol(7) together with 18 minor sterols. Examination of the aglycone moieties of the sterol-beta-xyloside fraction afforded 31 different sterols. Cholestan-3 beta-ol (15) and 24-methylcholesta-7,22-dien-3 beta-ol (20) were the major sterols in this group. Cholestanol sulfate (74) and cholesterol sulfate (64) were identified as the major components among the 34 different sterol sulfates present. Finally, cucumariosides G1 (1), C1 (2), C2 (3), H (4), and G2 (5) were isolated from the saponin fraction. Radiolabeling experiments indicated that there are two pathways of sterol biosynthesis in E. fraudratix. The first involves transformation of squalene to produce lanosta-9(11),24-dien-3 beta-ol(parkeol) which is subsequently demethylated to form 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol (6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol (7). The second proceeds through squalene to lanosterol which is further metabolized to produce the triterpene saponins, 5 alpha-cholest-7-en-3 beta-ol (19) and its xyloside (49).

The period from late 1949 through 1951 was an extraordinarily productive one in steroid chemistry and especially so at Syntex S.A. in Mexico City. Two of the most important Syntex contributions--the synthesis of 19-nor-17 alpha-ethynyltestosterone (norethindrone) and of cortisone from diosgenin--are described from a historical perspective.

A new cyclopropane-containing sterol was isolated from the marine sponge Cribrochalina vasculum. The new sterol was characterized by nuclear magnetic resonance and mass spectrometry and the structure was shown to be (23R,24S,28R)-dihydrocalysterol. Implications concerning the biosynthesis of cyclopropane and cyclopropene sterols in sponges are discussed.

An examination of the Australian sponge Phakellia aruensis led to the isolation and identification of sterols with six different nuclei. Eight new sterols were isolated which included three delta 15-A-nor sterols, three delta 7-A-nor sterols, and two saturated A-nor sterols. Their structures were established through mass spectrometry and 1H-NMR spectral studies.

Eighteen components of the sterol fraction of Pyrocystis lunula have been identified. In addition to 4 alpha-methyl sterols (typical dinoflagellate sterols), regular sterols, both with a saturated and delta 5-unsaturated skeleton, were isolated, together with delta 4-3-keto steroids including the hitherto unknown 23,24R-dimethyl-4,22E-cholestadien-3-one.

Sterols characterized by an allylic hydroxyl group in the side chain, such as stigmasta-5,28-diene-3 beta, 24 epsilon-diol (1), cholesta-5,23-diene-3 beta,25-diol (2) and cholesta-5,25-diene-3 beta,24 epsilon-diol (3), have been identified several times in various marine algae. Their origin was considered as doubtful: they could have been bona fide constituents of the alga, or be artifacts caused by autoxidation during the isolation process. We have shown that the dihydroxy steroids 2 and 3 can indeed be produced by the autoxidation of cholesta-5,24-dien-3 beta-ol (desmosterol) (5), but that they are nevertheless present in the taxonomic significance.

Comparison of the highfield 1HNMR spectrum of 4 alpha, 24-dimethyl-5 alpha-cholestan-3 beta-o1 isolated by open column adsorptive chromatography and reversed-phase HPLC from P. homomalla with those of the corresponding synthetic 24 alpha and 24 beta compounds demonstrate that the gorgonian natural product is purely 24 beta, the same C-24 configuration found in sterols related to dinosterol and gorgosterol. 360 MHz 1HNMR data are also reported for synthetic 4 alpha, 24 beta-dimethyl-5 alpha-cholest-22E-en-3 beta-o1 (another P. homomalla natural product). The use of 1HNMR correlations in assigning C-24 configurations of 24-methyl marine sterols possessing various nuclei is examined and discussed. Analyses of the methyl sterol components of P. homomalla are tabulated and discussed with regard to origin and plausible biosynthetic interrelationships in light of the C-24 configurational findings.

Twelve stanols possessing the rare 5 beta-dihydro nucleus have been isolated from the marine sponge Petrosia ficiformis. These stanols have not previously been encountered in any samples of P. ficiformis which we have examined and appear to be the result of bacterial metabolism of the endogenous sponge sterols.

The aim of this research was to establish the true composition of the 19-nor stanols isolated from the sponge Axinella polypoides and to determine accurate stereochemistry for each 19-nor stanol isolated. The following new 19-nor stanols were collected from this sponge: (i) (22E,24S)-24-methyl-19,27-bisnor-5 alpha-cholest-22-en-3 beta-ol, (ii) (22R,23R)-22,23-methylene-19-nor-5 alpha-cholestan-3 beta-ol, (iii) (24 xi)-24-propyl-19-nor-5 alpha-cholestan-3 beta-ol and (iv) (23R,24R)-23,24-dimethyl-19-nor-5 alpha-cholestan-3 beta-ol. The general structure and stereochemistry of all fifteen 19-nor stanols were established by analysis of the MS and H-NMR (300 MHz, CDCl3) data measured for each compound. The relative percentage of 19-nor stanols having delta 22 double bonds should be sufficient to suggest that this sponge could be a potential source of starting material for the partial synthesis of certain oral contraceptives, which also have a 19-nor steroid nucleus.

More than thirty monohydroxy sterols were detected in the marine sponge Petrosia ficiformis, ranging from the ubiquitous 24-norcholesta-5,22-dien-3 beta-ol to the C30 sterol, 24-propylidenecholesterol. A new minor sterol was isolated and shown by spectral analysis and comparison with a synthetic sample to be (24R)-24,26-dimethylcholesta-5,26-dien-3 beta-ol [26(29)-dehydroaplysterol] (12).

The isolation, structure determination and synthesis of ergosta-5, 24(28), 25-trien-3 beta-ol, as well as the synthesis of its 28-14C analog--a possible biosynthetic precursor of several marine sterols--is described.

24xi--Methylcholestane-3beta, 5alpha, 6beta, 12beta, 25-pentol 25-monoacetate has been isolated from an Alyconarian and its structure was established in part through extensive high resolution mass spectral and nmr studies and partly through the nonidentity of one of its degradation products with 24xi-methylcholestane-3beta, 5alpha, 6beta, 12alpha-tetrol synthesized from deoxycholic acid.

The first natural occurrence of 19-norcholestenone is reported, together with 17 sterols and one other delta 4-3-ketone in the extracts of the Californian gorgonian, Muricea californica (Aurivillius). Six additional demethyl sterols and five additional 4-monomethyl sterols which remain unidentified were also detected. Lipid extracts of M. californica from a winter and summer collection were split by various chromatographic methods into free sterol, steryl ester, and steryl conjugate fractions. Sterol compositions (determined by CG and CG-MS) of each fraction, subsequent to hydrolysis, are tabulated and discussed with respect to plausible origins of observed variations. The possible relationship of the Muricea 19-nor-steroidal ketone to other naturally occurring 19-nor-steroids is discussed.

3beta-Hydroxy sterols occurring at a concentration of at least 0.001% of the sterol mixtures of Pseudoplexaura porosa and Plexaura homomalla have been fractionated using a series of refined techniques and subsequently analyzed using combined gas chromatography-mass spectrometry (GC-MS) in the development of a procedure for examining the minor and trace components of marine sterol mixtures. A total of 49 sterols were found which spanned a molecular weight range of 274 to 440. In addition delta4-3-keto analogs of cholesterol, 24-methylcholesterol and gorgosterol were found in the extracts of P. homomalla. Initial separation of various natural sterol-containing conjugates and free sterols was found to have a number of advantages. Fractional digitonin precipitation and alumina column chromatography were found to possess greater sterol separation abilities than previously recognized. Many of the minor sterols were found to possess novel structures including a series of short side chain sterols, 19-nor sterols, 5beta-stanols and 4-monomethyl sterols for which structure elucidation work is continuing.

The isolation and structure elucidation of nine new trace sterols with highly branched side chains from a Pseudaxinyssa species from the Australian Great Barrier Reef are described.

Seventeen stanols with a variety of unusual side chains and possessing the rare 5 beta-dihydro nucleus have been isolated from the sponge Calyx nicaeensis. These stanols probably result from bacterial metabolism of the endogenous sponge sterols.

An x-ray crystal structure determination of a dinostanol from the dinoflagellate Protoceratium reticulatum and zooxanthellae from Orbulina universa was completed. The novel sterol was shown to be 3 beta-hydroxy-4 alpha, 23R,24R-trimethyl-5 alpha-cholestane and may be one of the molecular fossils found in sediment cores from the deepest Black Sea trench.

The free sterol mixture of the sponge Psammaplysilla purpurea was shown to contain aplysterol as the major constituent. In addition to other sterols such as 5,7-cholestadien-3beta-ol, cholesterol, 5alpha-cholestan-3beta-ol, 24epsilon-methylcholesta-5,22-dien-3beta-ol, 24epsilon--methylcholesterol, 24epsilon-ethylcholesta-5,22-dien-3beta-ol and 24,28-dehydroaplysterol, a new minor sterol was isolated and shown by spectral analysis as well as partial synthesis to be 3beta-hydroxy-26,27-bisnorcholest-5-en-24-one. The sterol mixture contains no other short side chain or 24-keto sterols except for small amounts of 3beta-hydroxypregn-5-en-20-one and 3beta-hydroxy-5alpha-pregnan-20-one.

The mass spectral fragmentation of a number of 17alpha-hydroxy-, 17alpha-acetoxy-, and 17alpha-methoxyprogesterones have been examined. Unlike other steroidal delta4-3-ketones, fragmentation reactions associated with the alpha,beta-unsaturated ketonic function are not particularly significant; rather, abundant ions are formed by decomposition processes occurring in and around ring D. Reactions of diagnostic significance include complete or partial loss of ring D, and elimination of the C-17 side chain (CH3CO), followed by loss of the C-17 oxygen function together with a hydrogen atom (H2O, CH3COOH, CH3OH).

The great demand for improved long-acting injectable steroid contraceptives, particularly in developing countries, and the relative lack of interest from the pharmaceutical industry to develop such products stimulated WHO to launch a synthetic and screening programme to find improved, safe and acceptable injectable preparations. More than 210 esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) have been prepared in university-based research laboratories situated mainly in developing countries, and then screened by NICHHD in animal models. The following three compounds, levonorgestrel butanoate, cyclopropylcarboxylate and cyclobutylcarboxylate, proved to be particularly long-acting when administered as microcrystalline suspensions. The overall strategy of this research and development programme is described.

Two new sterols, (24E)-24-n-propylidenecholesterol and 24 epsilon-n-propylcholesterol, were isolated from a cultured marine Chrysophyte. Since most of the steroids found in marine invertebrates are unchanged or modified sterols of algal or symbiotic origin, the discovery of these two unusual sterols in a unicellular alga grown under well-defined conditions contributes to our knowledge of sterols in marine food chains and offers a potential substrate for biosynthetic labeling experiments.

The free sterol mixture of the sponge Stylotella agminata contained a series of 3-hydroxymethyl-A-nor sterols of 5 alpha-cholestane, 5 alpha-cholest-22-ene, 24-methyl-5 alpha-cholestane, 24-ethyl-5 alpha-cholestane, and 24-ethyl-5 alpha-cholest-22-ene. A new cyclopropane-containing sterol was isolated and shown to be 3 epsilon-hydroxymethyl-A-nor-5 alpha-gorgostane. Sterols with conventional nuclei were also present as minor constituents;

The sterol mixture isolated from the marine alga Eutreptia viridis consists mainly of delta 5,7-dienes which account for 80% of the free sterols. Eighteen different sterols were detected, including a novel sterol with the rare delta 23-unsaturation, viz. 24-ethylcholesta-5,7,23Z-trien-3 beta-o1.