Determination of the Relative Configurations in the Side Chains of the Antibiotics Hedamycin and Pluramycin A; Synthesis and NMR. Data of Suitable Model Compounds

Several diepoxyhexanoates and epoxyhexenoates were prepared by epoxidation of methyl 2-methyl-2,4-hexadienoate or by Darzens condensation. Their ¹ H- and ¹³C-NMR. spectra were measured and assigned. Comparison of these data with the spectra of the antibiotics hedamycin ( 1 ) and pluramycin A ( 2 ) allowed the determi-nation of the relative configurations in the side chains of these antibiotics. They were found to be (14R*,16S*,17R*,18S*) for hedamycin ( 1 ) and (14R*,16S*,17Z) for pluramycin A ( 2 ).     

New Dolabellane Derivatives from the Brown Alga Dictyota pardalis

Reinvestigation of the brown alga Dictyota pardalis f. pseudohamata CRIBB led to the crystallization of 1 and to the isolation of the two new dolabellane derivatives 2 and 3 . X-Ray analysis of 1 and 2 , together with detailed 1D-and 2D-NMR studies on 2 and 3 , allowed their structures to be elucidated as (1R*,3S*,7S*,11R*,4Z)-dolabella-4,8(17), 12(18)-triene-3,7-diol ( 1 ), (1R*,3S*,4S*,7S*,8S*,11R*,14R*,12E)-3,4:7,8-diepoxydolabe11-12-ene-14, 18-diol ( 2 ), and (1R*,3S*,4S*,7S*,8S*,11R*,14R*)-3,4:7,8-diepoxy-l,4,8,12,12-pentamethylbicyclo[9. 3. 0]tetra-decan-14-ol( 3 ).     

Synthesis and structures of 1,1"-dialkyl-3,3"-bidiaziridines

First representatives of 3,3"-bidiaziridines, viz., 1,1"-dialkyl-3,3"-bidiaziridines, were synthesized and isolated as mixtures of two diastereomers. In the case of Alk = Me, the diastereomers were separated. It was demonstrated by nuclear Overhauser effect experiments and X-ray diffraction analysis that the diastereomers are the racemate (rac-1R*,2R*,3S*,1"R*,2"R*,3"S*) and the meso-form (1S*,2S*,3R*,1"R*,2"R*,3"S*).     

A novel glyceryl ester (glyceryl dendryphiellate A), a trinor-eremophilane (dendryphiellin A1), and eremophilanes (dendryphiellin E1 and E2) from the marine deuteromycete Dendryphiella salina (SUTHERLAND) PUGH et NICOT

Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites. Besides (22E)-ergosta-4.6,8(14),22-tetraen-3-one which, though known from basidiomycetes, was unknown in the sea, they are an unusual glyceryl ester, i.e. glycer-1-yl dendryphiellale A (= (+)-(2R)-2,3-dihydroxyprop-l-yl (6S,2E,4E)6-methylocta-2,4-dienoate; (+)- 1 ), a trinor-eremophilane, i.e. dendryphiellin A1 ( = (+)-(3R*,4E,6E)-7-{[(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2yl]oxycarbonyl}-3-methylhepta-4,6-dienoic acid; (+)- 11 ), and two eremophilanes, i.e. dendryphiellin El ( = (+)-(1R*, 2S*, 7S*,8aR*)-1,2,6,7,8,8a-hexahydro-1,8a-dimethyl-7-(1-methylethenyl)-6-oxonaphthalen-2-yl(6S,2E,4E)-6-methyl-octa-2,4-dienoate; (+)- 13 ) and dendryphiellin E2 ( = (+)-(1R*, 2S*, 8aR*)-1,2,6,7,8,8a-hexahydro-7-isopropyl-idene-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S,2E,4E)-6-Methylocta-2,4-dienoate; (+)- 14 ). Absolute configurations have been established for (+)- 1 via total synthesis and for the acid portion of (+)- 13 and (+)- 14 via transesterification in NaOMe/MeOH which gave in both cases melhyl dendryphiellate A ((+)- 16 ) of known configuration and the free alcoholic moiety of (+)- 14 , i.e. (+)- 17 .     

Studies on ketene and its derivatives. CXI . Photoreaction of diketene with 2(1H)-quinolone derivatives

Photoreaction of diketene with 4-methyl-2(1H)-quinolone and 1,4-dimethyl-2(1H)-quinolone gave 2R*,2aR*,SbR*- and 2R*,2aS*8bS*-8b-methyl-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline-2-spiro-2′-(oxetan)-4′-one ( 6a and 6b ), and their 4-methyl derivatives 7a and 7b , respectively. Thermolysis of compounds 6 and 7 afforded 2aR*,8bS*-8b-methyl-2-methylene-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]quinoline ( 8 ) and its 4-methyl derivatives 9 , respectively. Similarly, photolysis of diketene and 4-acetoxy-2(1H)-quinolone gave 1R*,2aS*,8bS*- and 1R*,2aR*,8bR*-8b-acetoxy-3-oxo-1,2,2a,3,4,8b-hexahydrocyclobuta[c]-quinoline ( 11a and 11b ). Alcoholysis of compounds 11a and 11b with hydrogen chloride in methanol gave 1-hydroxy-1-(methoxycarbonyl)methylcyclobuta[c]quinoline derivative 12 and 13 which were transformed to 4-acetyl-3-methyl-2(1H)-quinolone ( 15 ) by further alcoholysis. Photoreaction of diketene with 2(1H)-quinolone derivatives gave the corresponding cyclobuta[c]quinoline spirooxetanone derivatives 18 and 23 , which, by thermolysis, were transformed to 2-methylenecyclobuta[c]quinoline 23 and 25 , respectively.     

Leucascandrolide B,a New 16-Membered,Extensively Methyl-Branched Polyoxygenated Macrolide from the Calcareous Sponge Leucascandra caveolata from Northeastern Waters of New Caledonia

We report a novel, extensively methyl-branched and polyoxygenated 16-membered macrolide, leucascandrolide B (=(1R*,5S*,7R*,9S*,13R*,14R*,15R*,11Z)-5-[(E)-1,4-dimethylhept-5-enyl]-1,7,9-trihydroxy-11,14-dimethyl-3-oxo-4,17-dioxabicyclo[11.3.1]heptadec-11-en-15-yl] carbamate; 2 ), isolated from the calcareous sponge Leucascandra caveolata Borojevic and Klautau from the northeastern coast of New Caledonia. The NMR structural assignments were corroborated by semisynthetic derivatives of 2 , the functional groups and atom connectivity by derivatives 4 – 6 (obtained by acetylation, oxidation, and elimination-solvation, resp.), and the relative configurations by derivative 7 (obtained by carbonation). The preferred conformation of 2 , centered on a chair-like tetrahydro-2H-pyran ring formed by intramolecular acetalization, was derived from molecular mechanics and semiempirical calculations which were in agreement with all NMR data. A dilactone `dimeric' structure 3 , indistinguishable from 2 on the basis of all above data, was ruled out by tandem MS-MS experiments.     

A Novel Dimeric Podophyllotoxin‐Type Lignan and a New Withanolide from Withania coagulans

A novel dimeric lignan, bispicropodophyllin glucoside ( 1 ) and a highly oxygenated new withanolide, coagulin S ( 2 ) were isolated from the ethanolic extract of Withania coagulans. The structures were established on the basis of the spectroscopic data and have been identified as (5S*,5aR*,8aR*,9S*,15S*,15aS*,18aS*,19S*)‐9,19‐di‐β‐D ‐glucopyranosyl‐5,8a,9,15,15a,18,18a,19‐octahydro‐5,15‐bis(3,4,5‐trimethoxyphenyl)bis([1,3]dioxolo[4′,5′:6,7]naphtho)[2,3‐c:2,3‐h][1,6]dioxecin‐6,16(5aH,8H)‐dione ( 1 ) and (20S*,22R*)‐5α,6β,14α,15α,17β,20,27‐heptahydroxy‐1‐oxowith‐24‐enolide ( 2 ), respectively.     

New Sesquiterpenoids from Salvia castanea Diels f. tomentosa

Two new sesquiterpenoids, castanin A (= 4R*,5R*,5aS*,8S*,8aR*,8bR*)‐8‐formyl‐4,5,5a,6,7,8,8a,8b‐octahydro‐5,8b‐dihydroxy‐3,5a,8‐trimethyl‐2‐oxo‐2H‐indeno[4,5‐b]furan‐4‐yl acetate; 1 ) and castanin B (= 1aS*,6R*,6aS*,7aR*,9aR*)‐1a,2,6,6a,7a,8,9,9a‐octahydro‐1a,5,7a‐trimethylbisoxireno[4,5 : 8,9]cyclodeca[1,2‐b]furan‐6‐yl acetate; 2 ) were isolated from the aerial parts of Salvia castanea Diels f. tomentosa, together with two known compounds, oplophanone and 1β,6α‐dihydroxyeudesm‐4(14)‐ene. Their structures were elucidated by spectroscopic analyses and, in the case of 2 , also by X‐ray crystallography. Castanin A ( 1 ) represents a novel sesquiterpenoid, with a contracted ring A, derived from eudesmanolide. A possible biogenetic pathway is proposed.     

Coralloidolide A and Coralloidolide B,the First Cembranoids from a Mediterranean Organism,the Alcyonacean Alcyonium coralloides

The alcyonacean Alcyonium ( = Parerythropodium) coralloides (PALLAS 1766) is the first Mediterranean organism shown to contain cembranoids. These are of unusual type like coralloidolide A ( = (?)-(1R*, 2R*, 3R*, 12S*, 5Z, 7Z, 9Z)-1, 2:7, 10-diepoxy-12-isopropenyl-5, 9-dimethylcyclotetradeca-5, 7, 9-triene-1, 3-carbolactone; (?)-6) and coralloidolide B ( =(?)-(1R*,2S*,3R*,7S*,10S*,12S*,5Z,8Z,)-2, 7:7, 10-diepoxy-1, 10-dihydroxy-12-isopropenyl-5, 9-dimethylcyclotetradeca-5,8-diene-1,3-carbolactone; (?)-8). Structural assignments are mainly based on 1D- and 2D-NMR data and on chemical transformations.     

The Synthesis of a Novel Epoxycyclohexane from the Fungus Eutypa lata (Pers: F.) TUL

The synthesis of the novel (1′R*,2′S*,3′R*, 4′S*,5′R*)-1-(3′,4′-epxoy-2′, 5′-dihydroxycyclohexyl)-3-methyl-but-2-enone ( 2 ), recently isolated from the culture medium of the fungus Eutypa lata, is described.     

Aromastoffe der roten Passionsfrucht. Zwei neue Edulanderivate

Aroma Constituents of the Purple Passion Fruit. Two New Edulan Derivatives The isolation of (2R*, 4S*, 4aS*, 8aS*)-4,4a-epoxy-4,4a-dihydroedulan ( 1 ), and (2R*, 3S*, 8aS*)-3-hydroxyedulan ( 2 ), two new constituents of the purple passion-fruit (Passiflora edulis SIMS ), is reported. Racemic epoxide 1 was synthesized by oxidation of edulan 6 with peracidic acid, and racemate of alcohol 2 was obtained by reduction of ketone 7 , one of the chromic acid oxidation-products of edulan 6 .     

Bisabolane Derivatives from Leontopodium alpinum

From the roots of Leontopodium alpinum, four new bisabolane sesquiterpenoids, (1R*,2S*,4R*,5S*)‐4‐(acetyloxy)‐2‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐5‐methylcyclohexyl (2Z)‐2‐methylbut‐2‐enoate ( 1 ), (1R*,4S*,6R*)‐4‐(acetyloxy)‐6‐[3‐(acetyloxy)‐1,5‐dimethylhex‐4‐enyl]‐3‐methylcyclohex‐2‐en‐1‐yl (2Z)‐2‐methylbut‐2‐enoate ( 2 ), and 3‐methyl‐1‐{2‐[(1R*,2R*,5R*,6S*)‐2,5,6‐tris(acetyloxy)‐4‐methylcyclohex‐3‐en‐1‐yl]propyl}but‐2‐enyl (2Z)‐2‐methylbut‐2‐enoate ( 3 and 4 ) have been isolated. The latter constituents differ from each other by the relative configurations of the chiral centers of the hexenyl side chain.     

Two New Ceramides from the Marine Sponge Ircinia fasciculata

A new 4‐sulfated ceramide, ircisulfamide (=N‐[(1S*,2S*,3R*)‐2‐hydroxy‐1‐(hydroxymethyl)‐3‐(sulfooxy)heptadecyl]hexadecanamide; 1 ), and a new glycosphingolipid, ircicerebroside (=(2R*)‐N‐{(1S*,2R*,3E,7E)‐1‐[(β‐D ‐glucopyranosyloxy)methyl]‐2‐hydroxy‐8‐methylheptadeca‐3,7‐dienyl}‐2‐hydroxyeicosanamide; 2 ), were isolated from the aqueous EtOH extract of the marine sponge Ircinia fasciculata (Pallas ). The structures of the new compounds were elucidated on the basis of spectroscopic analysis and by means of chemical methods.     

Novel cembranolides (Coralloidolide D and E) and a 3,7-Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7-cyclized cembranoid Coralloidolide C ( = (+)-(6R*, 7R*, 11S*, 12aS* 3aE)-7,8-epoxy-3,5,6,7,8,9,10,11,12,12a-decahydro-12a-hydroxy-11-isopropenyl-1,4-dimethyl-3-oxocyciopentacydoundecene-8,6-carbolactone; (?)- 3 ), the O-bridged diketonic cembranolide Coralloidolide D (= (+)-(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)-2,5-epoxy-1-hydroxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetradeca-8-ene-1,3-carbolactone; (+)- 4 ), and the diketonic epoxycembranolide coralloidolide E (=(+)-(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)-1,2-epoxy-12-isopropenyl-5,9-dimethyl-7,10-dioxocyclotetra-deca-5,8-diene-1,3-carbolactone; (+)- 5 ), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (?)- 7 . Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((?)- 1 ) or the hypothetic unsaturated 1,4-diketone 9 can be envisaged as the precursors of all coralloidolides.     

Synthese von optisch aktiven Carotinoiden mit 3,5,6-Trihydroxy-5-6-dihydro-β-Endgruppen

Syntheses of Optically Active Carotenoids with 3,5,6-Trihydroxy-5,6-dihydro β-End Groups For the specification of the relative and absolute configuration in carotenoids with 3,5,6-trihydroxy-5-6-dihydro β-end groups, several ionone derivatives and carotenoids bearing this end group were synthesized. Acid-catalyzed hydrolysis of (3S,5S,6R)– acetoxy-5,6-epoxy-5,6-dihydro-β-ionone ( 7 ) and of its (3S,5R,6S)-isomer ( 13 ) gave the diols 8 and 15 , respectively, with exclusive inversion at c(5) (Scheme 2). Compared to this, mild acid hydrolysis of caroten-5-6-expoxides in the presence of H₂O resulted in the formation of 5,6-diols with either inversion or retention of the configuration at C(6) (Scheme 3). Spectroscopic data allowed us to distinguish the relative configurations (3R*,5S*,6S*) (see A ), (3R*,5R*,6R*) (see B ), (3R*,5S*,6R*) (see C ), and (3R*,5R*,6S*) (see D ), of the 3,5,6-trihydroxy-5-6-dihydro β-end groups. Syntheses of the optically active carotene-hexols 20 and 21 and comparison with published data led to a revision of the structure of mectrazanthin (now formulated as 20 ), heteroxanthin (now formulated as 28 ), and further carotenoids with 3,5,6-trihydroxy end groups.     

Slowly Interconverting Conformers of The Briarane Diterpenoids Verecynarmin B,C, and D,Isolated from the nudibranch mollusc Armina maculata and the pennatulacean octocoral Veretillum cynomorium of East Pyrenean waters

The novel briarane diterpenoids verecynarmin B(=(?)-(1R*, 10S*, 11R*, 4E, 12Z)-briara-4,7,12,17,-tetraen-14-one; (?)- 4 ); verecynarmin C (=(?)-(1R*, 10R*, 11S*, 4E, 12Z)?11-hydroxybriara-4,7,12,17-tetraen-14-one; (?)- 5 ); and verecynarmin D (=(?)-(1R*, 10R*, 11R*, 4E, 12E)-13-chloro-11-hydroxybriara-4,7,12,17,-tetraen-14-one; (?)- 6 ) are reported here as constituents of both the Mediterranean nudibranch mollusc Armina maculata (Rafinesque) and its prey, the pennatulacean octocoral Veretillum cynomorium (PALLAS ). The structural assignments rest mainly on (i) establishing that these briaranes occur in solution as two stable conformers which interconvert slowly (ca. 10 time per second at r.t. according to dynamic NMR) by 180° flipping of the C(4)?C(5) group in the ten-membered ring (Scheme 1), (ii) deriving, for both conformers, ¹H, ¹H coupling constants from 1D spectra, as well as ¹H, ¹H, ¹³C, ¹H, and ¹³C, ¹H, and ¹³C, ¹³C, correlations from 2D experiments; (iii) subjecting the briaranes to SeO₂ oxidation at the C(16) methyl group with isomerization at the C(4)=C(5) bond to give, in each case, only one observable molecular species as shown by NMR spectroscopy (Scheme 2).     

Novel Trinor-eremophilanes (Dendryphiellin B,C, and D), Eremophilanes (Dendryphiellin E,F, and G), and Branched C9-Carboxylic Acids (Dendryphiellic Acid A and B) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGHet NICOT

Further investigation of global extracts from cultures of the marine deuteromycete Dendryphiella salina leads to the isolation of three novel trinor-eremophilanes esterified by branched C₉-carboxylic acids, dendryphiellin B (= (+)-(1R*,2S*,7R*,8aR*)-1,2,6,7,8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*, 2E, 4E)-6-hydroxy-6-methylocta-2,4-dienoate; (+)- 2 ), dendryphiellin C (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7,8,8a-hexa-hydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6S, 2E, 4E)-6-methylocta-2,4-dienoate; (+)- 3 )), and dendryphiellin D (=(+)-(1R*, 2S*, 7R*, 8aR*)-1,2,6,7(8,8a-hexahydro-7-hydroxy-1,8a-dimethyl-6-oxonaphthalen-2-yl (6R*,2E,4E)-6-(hydroxymethyl)octa-2,4-dienoate; (+)- 4 ). An intact eremophilane, dendryphiellin E ( 5 ), and its ethanolysis product dendryphiellin F whose absolute configuration is represented by structural formula (+)- 6 are also isolated from the above extracts. Dendryphiellin E exists as an open form 5a in equilibrium with a closed form 5b . A similar equilibrium exists between the open form 8a and the closed form 8b of a non-esterified eremophilane, dendryphiellin G ( 8 ), which is isolated too from the above extracts and proves structurally related to the cyclic portion of 5 . Finally, the free, branched C₉-carboxylic acids dendryphiellic acid A ((+)- 9 ) and B ((+)- 10 ) which correspond to side chains of the above esterified terpenes are also isolated from the above extracts.     

Acetogenins from the Leaves of Rollinia laurifolia

From the EtOH extract of the leaves of Rollinia laurifolia Schl . (Annonaceae), a novel acetogenin, rolifolin (= 3‐(9‐{(2R*,5S*)‐5‐[(1S*,4S*)‐1,4‐dihydroxy‐4‐{(2S*,5R*)‐5‐[(1S*)‐1‐hydroxyundecyl]tetrahydrofuran‐2‐yl}butyl]tetrahydrofuran‐2‐yl}‐2,3‐dihydroxynonyl)‐5‐methylfuran‐2(5H)‐one; 1 ) was isolated, together with the known acetogenin annonin‐I ( 2 ). Also, from the corresponding hexane extract, a mixture of rolilaurin ( 3 , a novel compound), uvariamicin‐I ( 4 ), and uvariamicin‐II ( 5 ) was obtained. The structures of compounds 1 – 5 were elucidated by NMR and MS analysis, and relative configurations were established. Compounds 2 and 5 have never been obtained before from Rollinia.     

A new cytotoxic isocoumarin from endophytic fungus <Emphasis Type="Italic">Penicillium</Emphasis> SP. 091402 of the mangrove plant <Emphasis Type="Italic">Bruguiera sexangula</Emphasis>

A new isocoumarin, (3R*,4S*)-6,8-dihydroxy-3,4,7-trimethylisocoumarin (1), and five known compounds were isolated from mangrove endophytic fungus Penicillium sp. 091402. The structures of all the compounds were elucidated by analysis of spectrometric data.     

Packing in three cyclooctitol acetates

Three cyclooctitol derivatives, in the form of a tetraacetate, (1S*,2R*,3S*,4S*)‐2,3,4‐triacetoxycyclooctan‐1‐ylmethyl acetate, C₁₇H₂₆O₈, and two regioisomeric acetonide triacetates, (3aS*,4R*,8S*,9S*,9aS*)‐8,9‐diacetoxy‐2,2‐dimethylcyclooctano[d][1,3]dioxan‐4‐ymethyl acetate and (3aS,4R,7S,9R,9aS)‐7,9‐diacetoxy‐2,2‐dimethylcyclooctano[d][1,3]dioxan‐4‐ylmethyl acetate, both C₁₈H₂₈O₈, have been studied. The conformation of the cyclooctane ring in the three compounds is quite close to the boat–chair form of the parent hydrocarbon. Packing is effected through weak C—H...O and van der Waals contacts.