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.     

A convenient and diastereoselective route to homoallyl alcohols: Addition of (z)- or (e)-alkenyl-dimethoxyboranes to aldehydes

(Z)-2-Butenyl-dimethoxyborane adds smoothly to propanal and benzaldehyde to afford the homoallyl alcohols (R*,R*)- 1 and (R*,R*)- 2 , In contrast (E)-2-butenyl-dimethoxyborane leads to adducts having the (R*,S*)-configuration. Dimethoxy-(Z)-2-pentenylborane, dimethoxy-(Z)-(2-methyl-2-butenyl)borane and (2Z,4E)-or (2E,4Z)hexadienyl-dimethoxyborane, treated with propanal, give (R*,R*)- 3 , (R*,R*)- 4 , (E),(R*,S*)- 5 and (Z),(R*, R*)- 5 , respectively. A transition state model implying a pericyclic electron motion is in perfect agreement with the regio- and stereoselective outcome of these borane reactions.     

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.     

Regioselectivity in the formation of norbornene-fused pyrazoles: preparation of 1-substituted derivatives of 4,5,6,7-tetrahydro-1H-4,7-methanoindazole

The structural characteristics of (±)-(exo,exo)-3-(hydroxymethylene)-5,6-(isopropylidenedioxy)bicyclo[2.2.1]heptan-2-one make the reactions between this β-diketone and hydrazines particularly interesting for elucidating the mechanism of pyrazole formation. The isolation and X-ray structure determination of two 5-hydroxy substituted Δ²-pyrazolines [(±)-(3aR*,4R*,5R*,6S*,7R*,7aR*)-7a-hydroxy-5,6-(isopropylidenedioxy)-3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-indazole] and [(±)-(3aS*,4R*,5R*,6S*,7R*,7aR*)-7a-hydroxy-5,6-(isopropylidene-dioxy)-1-phenyl-3a,4,5,6,7,7a-hexa-hydro-4,7-methano-1H-indazole] has been determinant for proposing a mechanism. Besides B3LYP/6-31G* calculations have been carried out on all intermediate dihydroxypyrazolidines and 5-hydroxypyrazolines. Finally, the annular tautomerism of the NH-methanotetrahydroindazoles has been studied both experimentally (¹³C NMR) and theoretically: the Mills-Nixon effect favours the 2H-tautomer.     

Five-membered 2,3-dioxo heterocycles: LXXVII. [4 + 2]-Cycloaddition of alkyl vinyl ethers to 3-aroylpyrrolo[2,1-<Emphasis Type="Italic">c</Emphasis>][1,4]benzoxazine-1,2,4(4<Emphasis Type="Italic">H</Emphasis>)-triones

[4 + 2]-Cycloaddition of 3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4(4H)-triones to alkyl vinyl ethers gave substituted stereoisomeric (1R*,16R*)- and (1S*,16R*)-16-alkoxy-14-aryl-3,15-dioxa-10-azatetracyclo[8.7.0.0^{1, 13}.0^{4, 9}]heptadeca-4,6,8,13-tetraene-2,11,12-triones.     

Coralloidin C,D, and E: Novel Eudesmane Sesquiterpenoids from the Mediterranean Alcyonacean Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium (=Parerythropodium) coralloides (Pallas, 1766) is shown to contain the novel eudesmane sesquiterpenoids coralloidin C (=(–)?(4R,10S)-eudesma-5,7(11)-dien-15-yl acetate; (–)? 4 ), coralloidin D (=(–)?(10R*)-eudesma-4,7(11)-diene-12,13-diyl diacetate; (–)? 7 ), and coralloidin E (=(+)?(4R*,10R*)-eudesma-5,7-dien-11-ol;(+)? 8 ). The absolute configuration of (–)? 4 is derived by the exciton-coupling method, applied to deacetylcoralloidin C_p-anisate ((–)? 6 ). Coralloidin E((+)? 8 ), being also obtained on treatment of deacetylcoralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-ol; (+)? 2 ) with (COCl)₂ in DMSO, is configurationally correlated to coralloidin A (=(+)?(4R*, 8R*, 10R*)-eudesma-5,7(11)-dien-8-yl acetate; (+)? 1 ). Under acidic conditions, (+)? 2 undergoes a complex rearrangement giving (+)-(3R*, 4S*, 5R*, 6R*, 7S*)-arist-10-(1)-en -3-ol ((+)? 9 ), which is also obtained, together with (+)? 8 , on attempts to mesylate (+)? 2 .     

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.     

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.     

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.     

Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

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 .     

Tautomeric and conformational equilibria of γ-lactones derived from (3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetic acid

Tautomeric transformation of (3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetic acid into previously unknown stereoisomeric γ-lactones, (3aS*,7S*,7aR*)- and (3aS*,7R*,7aR*)-5,7-dibromo-3ahydroxy-3,3a,7,7a-tetrahydro-1-benzofuran-2,6-diones, was revealed by ¹H NMR spectroscopy. The concentration of the acid tautomer increases as the solvent polarity rises. The ability of the cycloxexene ring in the lactones to undergo inversion in solution is determined by orientation of the bromine atom on C⁷.     

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.     

Coralloidolide F,the First Example of a 2,6-Cyclized Cembranolide: Isolation from the Mediterranean Alcyonacean Coral Alcyonium coralloides

The Mediterranean alcyonacean Alcyonium ( = Parerythropodium) coralloides (Pallas, 1766) is shown here to contain coralloidolide F ( = (+)-(3a-R*, 7R*, 8R*, 9R*, 12R*, 12aS*)-8,9-epoxy-1,3a,6,7,8,9,10,11,12,12a-decahydro-3a-hydroxy-12-isopropenyl-2,5-dimethyl-1-oxocyclopfintacycloundecene-9,7-carbolactone; (+)- 2 ), the first example of a 2,6-cyclized cembranolide. Structural assignments are mainly based on ID and 2D NMR and MS data.     

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 .     

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.     

The reactivity of N,N-dialkyl-N-(3-phenylsulfinyltetrahydrofuran-2-ylidene)ammonium bromide

trans-Stereoselective electrophilic cyclization of (2R*,SS*)-N, N-diisopropyl-2-phenylsulfinylpent-4-enamide under the action of bromine afforded (3R*,5S*, SS*)-N-(5-bromomethyl-3-phenylsulfinyltetrahydrofuran-2-ylidene)-N,N-diisopropylammonium bromide. Its transformations under the conditions of hydrolysis, dehydrobromination, and hydride reduction were studied. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1485–1490, August, 2007.     

Synthesis of (5R*)- and (5S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-ones

Heating of N-benzoyl-N-[2-(1-methylbut-2-en-1-yl)-4-methylphenyl]glycine with ethyl chloroformate or acetic anhydride gave (5R*) and (5S*) isomers of (1R*,3aS*,4S*,11S*)-5,7,11-trimethyl-3a-phenyl-4,5-dihydro-3aH-1,4-methano[1,3]oxazolo[3,2-a]quinolin-2-one.     

The Structure of Diastereomeric Oxaprotiline Metabolites. An NMR Study

The structure of phenolic metabolites of oxaprotiline, obtained from a study with rats and dogs, are assigned with NMR-spectroscopic methods in combination with MS data and an X-ray structure analysis of synthetic (9R*,2′S*)-2-chlorooxaprotiline, the metabolites are shown to be (9R*,2′R*)-2-hydroxy, 3-hydroxy-, and 2-hydroxy-3-methoxyoxaprotiline, and (9R*,2′S*)-2-hydroxy-, 3-hydroxy-, and 3-hydroxy-2-methoxyoxaprotiline, as well as 2,6-dihydroxyoxaprotiline.     

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.