A new pyrrolidine derivative and steroids from an algicolous Gibberella zeae strain

A new pyrrolidine derivative, 3-hydroxy-5-(hydroxymethyl)-4-(4'-hydroxyphenoxy)pyrrolidin-2-one (1), and eight known steroids, (22E,24R)-7beta,8beta-epoxy-3beta,5alpha,9alpha-trihydroxyergosta-22-en-6-one (2, a reassigned structure of (22E,24R)-5alpha,6alpha-epoxy-3beta,8beta,14alpha-trihydroxyergosta-22-en-7-one), (22E,24R)-3beta,5alpha,9alpha-trihydroxyergosta-7,22-dien-6-one (3), (22E,24R)-3beta,5alpha-dihydroxyergosta-7,22-dien-6-one (4), (22E,24R)-ergosta-7,22-dien-3beta/,5alpha,6beta-triol (5), (22E,24R)-ergosta-5,22-dien-3beta-ol (6), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (7), (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9(11),22-trien-3beta-ol (8), and (22E,24R)-1(10 --> 6)-abeo-ergosta-5,7,9,22-tetraen-3alpha-ol (9), were isolated from the cultures of Gibberella zeae, an endophytic fungus isolated from the marine green alga Codium fragile. Their structures and relative stereochemistry were elucidated by 1D, 2D NMR and mass spectroscopic techniques. Compound 1 showed cytotoxicity against A-549 and BEL-7402 cell lines.     

Three new glycosides from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO

Three new glycosides, 7-deoxyloganic acid beta-D-glucopyranosyl ester (1), (3R)-hydrangenol 8,4'-di-O-beta-D-glucopyranoside (2), and (6R,7E,9R)-megastigma-4,7-dien-3-one 9,13-di-O-beta-D-glucopyranoside (3), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO (Saxifragaceae). The structures of 1-3 were elucidated on the basis of spectral data and chemical evidence.     

Two new homoisoflavonoids from Caesalpinia pulcherrima

Two new homoisoflavonoids, (E)-7-methoxy-3-(4'-methoxybenzylidene)chroman-4-one (1) and (E)-7-hydroxy-3-(3',4',5'-trimethoxybenzylidene)chroman-4-one (5), along with three known homoisoflavonoids (Z)-7-hydroxy-3-(4'-methoxybenzylidene)chroman-4-one (isobon ducellin) (2), (E)-7-hydroxy-3-(4'-methoxybenzylidene)chroman-4-one (bonducellin) (3) and (E)-7-hydroxy-3-(2',4'-dimethoxybenzylidene)chroman-4-one (4) were isolated from the whole plant of Caesalpinia pulcherrima. The structures of these new compounds were elucidated by electron impact mass spectrometry (EI-MS) and 1D and 2D-NMR spectral studies. Antimicrobial activity of the new compounds was evaluated.     

Megastigmane glucosides from Equisetum debile and E. diffusum

A new megastigmane diglucoside, (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3,9-O-beta-D-diglucopyranoside (3), was isolated from the aerial portion of Equisetum debile along with macarangioside D (debiloside A), sammangaoside A, (6R,9S)-3-oxo-alpha-ionol 9-O-beta-D-glucopyranoside, debiloside B, kaempferol 3-O-sophoroside, kaempferol 3,7-O-beta-D-diglucopyranoside, kaempferol 3-O-sophoroside-7-O-beta-D-glucopyranoside, phenylethyl O-beta-D-glucopyranoside, (Z)-3-hexenyl O-beta-D-glucopyranoside, (7S,8R)-dehydrodiconiferyl 4-O-beta-D-glucopyranoside, and L-tryptophan. The absolute configuration at C-6 of the original structure of debilo-side A was revised to 6R-configuration, and was identical with macarangioside D (1). From the aerial portion of E. diffusum, four compounds, sammangaoside A, kaempferol 3-O-sophoroside and L-tryptophan and (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside were identified. The spectroscopic data of (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside (13) were found to be identical with corchoionoside A (9R-isomeric compound). The structure of corchoionoside A was also discussed. Structure determinations were based on physical data and spectroscopic evidence.     

Microbial transformation of diosgenin by Syncephalastrum racemosum (Cohn) Schroeter

<正>Microbial transformation of diosgenin(1) by Syncephalastrum racemosum yielded five new polar metabolites,which wereidentified as(25R)-spirost-5-en-3β,7α,9α-triol-12-one(2),(25R)-spirost-5-en-3β,9α,12α-triol-7-one(3),(25R)-spirost-5-en-3β,9α-diol-7,12-dione(4),(25R)-spirost-4-en-9α,12β,14α-triol-3-one(5),and(25S)-spirost-4-en-9α,14α,25β-triol-3-one(6).Compounds 1-6 exhibited moderate cytotoxicity against K562 cells and among them compounds 2,3,and 6 were more potentthan the parent compound 1.     

Constructing conformationally constrained macrobicyclic musks

To investigate the structure-odor correlation of musks, (12R)-12-methyl-13-tridecanolide (1), a macrocyclic musk, and 13-tridecanolide, its non-musky demethyl analogue, were conformationally constrained by introduction of methylene bridges between C-3 and C-8 or C-9. These [7.5.1]- and [8.4.1]-macrobicycles were synthesized starting from bicyclo[5.3.1]undec-8-en-9-one (3) and bicyclo[4.3.1]dec-7-en-8-one (8), respectively, by a sequence consisting of catalytic hydrogenation, alpha-alkylation with a TBS-protected (tert-butyldimethylsilyl) hydroxy halide, acid-catalyzed cyclization, oxidative cleavage of the formed enol ether double bond, and subsequent reduction of the carbonyl group via its tosylhydrazone. The compound (1R,6R,9R)-(+)-6-methyl-4-oxa-bicyclo[7.5.1]pentadecan-3-one (22) was found to possess the most pronounced musk odor, and this was rationalized by a superposition analysis with the polycyclic aromatic musk odorant (4S,7R)-Galaxolide (2). In its (1S,6R,9S)-(+)-stereoisomer 23 as well as in (1S,6R, 10R)-(+)-6-methyl-4-oxabicyclo[8.4.1]-pentadecan-3-one (18) the (6R)-methyl group seems to hinder the interaction with the musk receptor, while the demethyl compounds 7 and 12 showed only very faint odors.     

Construction of Chiral One-dimensional Chains via Mononuclear Chiral Precursors and Circular Dichroism Properties

One-dimensional(1D) chiral chain complexes [CuLSCu(Pydc)](2S) and [CuLRCu(Pydc)](2R)(LS=(E)-3-(((1S,2S)-2-(((E)-3-oxo-3-(4-pyridin-4-yl)phenyl)propylidene)amono)-1,2-diphenyl)imino)-1-(4-(pyridi-4-yl)phenyl)butan-1-one) and LR=(E)-3-(((1R,2R)-2-(((E)-3-oxo-3-(4-pyridin-4-yl)phenyl)propylidene)amono)-1,2-diphenyl)imino)-1-(4-(pyridi-4-yl)phenyl)butan-1-one and Pydc=2,6-pyridinedicarboxylic acid)have been synthesized vis mononuclear chiral enantiomer precursors CuLS(1S) and CuLR(1R).Their different chiral configurations of 1S,1R,2S and 2R were determined by single-crystal X-ray diffraction analyses and further characterized by elemental analyses,infrared spectra(IR),powder X-ray diffraction(PXRD),thermal gravimetric analyses(TGA) and circular dichroism spectra(CD).     

Asporyergosterol, a new steroid from an algicolous isolate of Aspergillus oryzae

Asporyergosterol (1), a new steroid with an E double bond between C-17 and C-20, was identified from the culture extracts of Aspergillus oryzae, an endophytic fungus isolated from the marine red alga Heterosiphonia japonica. Moreover, four known steroids including (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (2), (22E,24R)-3beta-hydroxyergosta-5,8,22-trien-7-one (3), (22E,24R)-ergosta-7,22-dien-3beta,5alpha,6beta-triol (4), and (22E,24R)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (5) were isolated. Structures of these compounds were unambiguously established by spectroscopic techniques and by comparison with literature values. All the isolates exhibited low activity to modulate acetylcholinesterase (AChE).     

Steroids and an oxylipin from an algicolous isolate of Aspergillus flavus

A new oxylipin, (8E,12Z)-10,11-dihydroxyoctadeca-8,12-dienoic acid (1), a new steroid, 3β,4α-dihydroxy-26-methoxyergosta-7,24(28)-dien-6-one (2), and four known steroids, episterol (3), (22E,24R)-ergosta-7,22-dien-3β,5α,6α-triol (4), (22E,24R)-ergosta-5,22-dien-3β-ol (5), and (22E,24R)-ergosta-4,6,8(14),22-tetraen-3-one (6), were isolated from the cultures of Aspergillus flavus, an endophytic fungus isolated from the marine red alga Corallina officinalis. Their structures and relative stereochemistry were elucidated by 1D, 2D NMR and mass spectroscopic techniques. 1 and 2 exhibited low activity to inhibit acetylcholinesterase and no activity against plant pathogenic fungi Colletotrichum lagenarium and Fusarium oxysporum.     

Preparation of (4′S) and (4′R)-Spiro(oxirane-2-4′-5α-cholestan-3′β-ol), Potent Inhibitors of 4-Methyl Sterol Oxidase

(4′R)- and (4′S)-Spiro(oxirane-2,4′-5α-cholestan-3′β-ol) (1) and (2) were made from (4′R)- and (4′S)-spiro(oxirane-2,4′-5α-cholestan-3-one) (8) and (9). Alkaline hydrogen peroxide oxidation of 4-methylene-5α-cholestan-3-one (7) gave compounds (8) and (9) as a readily separable (1:1) mixture. Reduction of (9) to (2) provided access to a compound which could not be made by other methods.     

An efficient enzymatic synthesis of benzocispentacin and its new six- and seven-membered homologues

A very efficient enzymatic method was developed for the synthesis of new enantiomeric benzocispentacin and its six- and seven-membered homologues through the Lipolase (lipase B from Candida antarctica) catalyzed enantioselective (E > 200) ring opening of 3,4-benzo-6-azabicyclo[3.2.0]heptan-7-one, 4,5-benzo-7-azabicyclo[4.2.0]octan-8-one, and 5,6-benzo-8-azabicyclo[5.2.0]nonan-9-one with H2O in iPr2O at 60 degrees C. The (1R,2R)-beta-amino acids (ee > or = 96%, yields > or = 40%) and (1S,6S)-, (1S,7S)-, and (1S,8S)-beta-lactams (ee > 99%, yields > or = 44%) produced could be easily separated. The ring opening of racemic and enantiomeric beta-lactams with 18% HCl afforded the corresponding beta-amino acid hydrochlorides.     

New Monoterpene-Substituted Dihydrochalcones from Piper aduncum

Five New unusual monoterpene-substituted dihydrochalcones, the adunctins A–E (1″S)-1-{2′-hydroxy-4′-methoxy-6′-[4″-methyl-1″-(1?-methylethyl)cyclohex-3″ -en-1″ -yloxy]phenyl}-3-phenylpropan-1-one ( 1 ), (5aR*,8R*,9aR*)-3-phenyl-1-[5′,8′,9′,9′a-tetrahydro-3′-hydroxy-1′-methoxy-8′-(1″-methylethyl)-5′-a-methyldibenzo-[b,d]furan-4′-yl]propan-1-one ( 2 ), (2′R*,4″S*)-1-{6′-hydroxy-4′-methoxy-4″-(1?-methylethyl)spiro[benzo[b]-furan-2′(3′H),1″ -cyclohex-2″ -en]-7′-yl}-3-phenylpropan-1-one ( 3 ), (2′R*,4″R*)-1-{6′-hydroxy-4′-methylethyl-4″-(1?-methylethyl)spiro[benzo[b]furan-2′(3′H),1″-cyclohex-2″-en]-7′-yl}-3-phenypropan-1-one ( 4 ), and (5′aR*,6′S*, 9′R*,9′aS*)-1-[5′a,6′,7′,8′,9′a-hexahydro-3′,6′-methoxy-6′-methyl-9′-(1″-methylethyl)dibenzo[b,d]-furan-4′-yl]-3-phenylpropan-1-one ( 5 ) were isolated from the leaves of Piper aduncum (Piperaceae) by preparative liquid chromatography. In addition, (?)-methyllindaretin ( 6 ), trans-phytol, and α-tocopherol ( = vitamin E) were also isolated and identified. The structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The antibacterial and cytotoxic potentials of the isolates were also investigated.     

Conformationally constrained dipeptide surrogates with aromatic side-chains: synthesis of 4-aryl indolizidin-9-one amino acids by conjugate addition to a common alpha,omega-diaminoazelate enone intermediate

Four methyl 9-oxo-8-(N-(Boc)-amino)-4-phenyl-1-azabicyclo[4.3.0]nonane carboxylates (11, 4-Ph-I(9)aa-OMe) were synthesized from (2S,8S,5E)-di-tert-butyl-4-oxo-5-ene-2,8-bis[N-(PhF)amino]azelate [(5E)-7, PhF = 9-(9-phenylfluorenyl)] via a seven-step process featuring a conjugate addition/reductive amination/lactam cyclization sequence. Various nucleophiles were used in the conjugate addition reactions on enone (5E)-7 as a general route for making alpha,omega-diaminoazelates possessing different substituents in good yield albeit low diastereoselectivity except in the case of aryl Grignard reagents (9/1 to 15/1 drs). 6-Phenylazelates (6S)-8d and (6R)-8d were separated by chromatography and diastereoselective precipitation and independently transformed into 4-Ph-I(9)aa-OMe. From (6S)-8d, (2S,4R,6R,8S)-4-Ph-I(9)aa-OMe 11 was prepared selectively in 51% yield. Reductive amination of (6R)-8d provided the desired pipecolates 9 along with desamino compound 10, which was minimized by performing the hydrogenation in the presence of ammonium acetate. Subsequent ester exchange, lactam cyclization, and amine protection provided three products (2R,4S,6S,8R)-, (2R,4S,6S,8S)-, and (2S,4S,6R,8S)-4-Ph-I(9)aa-OMe 11 in 10, 6, and 6% yields, respectively, from (6R)-8d. Ester hydrolysis of (2S,4R,6R,8S)-11 furnished 4-phenyl indolizidin-9-one N-(Boc)amino acid 3 as a novel constrained Ala-Phe dipeptide surrogate for studying conformation-activity relationships of biologically active peptides.     

Turpinionosides A-E: megastigmane glucosides from leaves of Turpinia ternata Nakai

From leaves of Turpenia ternata (Staphylaceae), one megastigmane and seven of its glucosides (1-8) were isolated. Megastigmane and two of the glucosides were found to be known compounds, namely, 3S,5R,6R,9S-tetrahydroxymegastigmane (1), corchoionoside C (2), and icariside B4 (3). The structures of compounds 4-8 (turpinionosides A-E, respectively) were elucidated by means of spectroscopic analyses, and then their absolute structures were determined by the modified Mosher's method to be (3S,5R,6S,9S)-3,6,9-trihydroxymegastigman-7-ene 3-O- and 9-O-beta-D-glucopyranosides (4, 5, respectively), (1S,3S,5R,6S,9R)-3,9,12-trihydroxymegastigmane 3-O-beta-D-glucopyranoside (6), (3S,4R,9R)-3,4,6-trihydroxymegastigman-5-ene 3-O-beta-D-glucopyranoside (7), and (2S,9R)-2,9-dihydroxymegastigman-5-en-4-one 2-O-beta-D-glucopyranoside (8).     

Antimalarial and cytotoxic activities of bicycl

Biological evaluations of bicyclo[6.4.0]dodecenone derivatives on antimalarial activity in vitro against Plasmodium falciparum and cytotoxicity against human KB cells were made. (+/-)-(1R*,4S*,7R*,8S*)-4-tert-Butyl-dimethylsiloxy-5,5-dimethyl-1-methyl-9-methylene-7-phenylsulfonylbicyclo[6.4.0]dodec-2,11-dien-10-one (15) exhibited potent antimalarial activity, whereas (+/-)-(1R*,7R*,8S*)-1-methyl-9-methylene-7-phenylsulfonylbicyclo[6.4.0]dodec-2,11-dien-10-one (14) showed significant cytotoxic activity in human KB cells. Both 14 and 15 possess, as a structural character, the exo-methylene moiety in their 6-membered ring of the 8-6 fused ring system.     

Novel steroids from the seeds of Centratherum anthelminticum

Two novel and two known steroids were isolated respectively from benzene: acetone and ethanolic extracts of the seeds of C. anthelminticum and, identified as (24alpha/R)-Stigmasta-7-en-3-one (1), (24alpha/R)-Stigmasta-7, 9(11)-dien-3-one (2), (24alpha/S)-Stigmasta-5, 22-dien-3beta-ol (3) and (24alpha/S)-Stigmasta-7, 22-dien-3beta-ol (4). The structures were assigned on the basis of their IR, 1H NMR, 13C NMR (DEPT), 2D NMR (1H-1H COSY and 1H-13C COSY), mass spectra, chemical analyses and on comparison with literature values. The novel steroids (1) and (2) were also tested against several human pathogenic bacteria and fungi.     

Synthesis of enantiopure 7-[3-azidopyl]indolizidin-2-one amino acid. A constrained mimic of the peptide backbone geometry and heteroatomic side-chain functionality of the ala-lys dipeptide

Enantiopure N-(BOC)amino-7-[3-azidopropyl]indolizidin-2-one acid 1 has been synthesized by displacement of the methanesulfonate of its 7-hydroxypropyl counterpart 11 with sodium azide and subsequent ester hydrolysis. N-(BOC)Amino-7-[3-hydroxypropyl]indolizidin-2-one ester 11 was obtained from a sequence commencing with the alkylation of (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(PhF)amino]azelate 5 (PhF = 9-(9-phenylfluorenyl)). Stereoselective allylation of 5, regioselective olefin hydroboration, selective primary alcohol protection as a silyl ether, and oxidation of the secondary alcohol gave (2S,4R,8S)-di-tert-butyl 4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into the indolizidinone heterocycle by a route featuring reductive amination, lactam cyclization, and isolation by way of a silyl ether which provided the (6S,7R)-isomer of 11.     

Design, synthesis, and 1,3-dipolar cycloaddition of (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1,4-oxazin-2-one N-oxides as chiral (E)-geometry-fixed alpha-alkoxycarbonylnitrones

Optically pure (5R)- [and (5S)]-5,6-dihydro-5-phenyl-2H-1, 4-oxazin-2-one N-oxides [(5R)- and (5S)-2] were designed as chiral (E)-geometry-fixed alpha-alkoxycarbonylnitrones 1. The nitrones (5R)- and (5S)-2 were synthesized by three-step oxidation of (R)- and (S)-phenylglycinols [(R)- and (S)-3], condensation of the resulting (R)- and (S)-2-hydroxylamino-2-phenylethanols [(R)- and (S)-5] with glyoxylic acid, and cyclization of the intermediary nitrones (R)- and (S)-6b. The nitrone (5R)-2reacted with olefins 7-14 under mild conditions to afford the corresponding cycloadducts 15-22 as the main products via the least sterically demanding exo modes. Cycloadduct 30 obtained from (5S)-2 and cyclopentadiene was effectively elaborated to (1S,4S, 5R)-4-benzyloxycarbonylamino-2-oxabicyclo[3.3.0]oct-7-en-3-one (28), the key synthetic intermediate of carbocyclic polyoxin C.     

Synthesis of Gingerenone C and 5-Hydroxy-1-(4'-hydroxy- 3'-methoxyphenyl)-7-(4"-hydroxyphenyl)-3-heptanone

The two diarylheptanoids (E)-1-(4'-hydroxy-3'-methoxyphenyl)-7-(4"-hydroxyphenyl) hept-4-en-3-one 1 (Gingerenone C) and (±)-5-hydroxy-1-(4'-hydroxy-3'-methoxyphenyl)-7-(4"-hydroxyphenyl)-3-heptanone 2 were synthesized from vanillin 3 and 4-hydroxybenzaldehyde 9.     

Polyoxygenated ergostane-type sterols from the liquid culture of Ganoderma applanatum

A new polyoxygenated ergostane-type sterol, 3β,5α,6β,8β,14α-pentahydroxy-(22E,24R)-ergost-22-en-7-one (1), has been isolated from the liquid culture of the basidiomycete Ganoderma applanatum together with four known sterols, 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2), ergosterol peroxide (3), 6-dehydrocerevisterol (4) and cerevisterol (5). Two of these sterols (2, 4) are reported to have been isolated from this species for the first time. The structures of these compounds were determined by chemical and spectroscopic analyses, including 1D- and 2D-NMR, as well as by comparison of their spectroscopic data with those reported in the literature.