胆甾-4α-甲基-8-烯-3β，7α-二醇二乙酸酯的结构与性质研究

Lophenol, cholest-4α-methyl-7-en-3β-ol (1), obtained from Dracaena cochinchinensis (Lour.) S. C. Chen, was structurally modified. It was acetylated to protect 3β-hydroxyl group, and then oxidised by selenium dioxide in acetic acid to give cholest-4a-methyl-8-en-3β, Ta-diol diacetate (3). This compound 3 is unstable in chloroform solution or when heated and easily converted to a diene compound, cholest-4a-methyl-7,14-dien-3β-ol acetate (4). The structures of 3 and 4 were elucidated by means of IR, ^1H NMR, ^13C NMR and MS, and the absolute configuration of 3 was established by X-ray crystallography. The property of 3 was also discussed in this paper. Both 3 and 4 are new compounds and were reported for the first time.     

New α‐Tetralone Galloylglucosides from the Fresh Pericarps of Juglans sigillata

Three new α‐tetralone galloylglucosides, 1 – 3 , were isolated from the fresh pericarps of Juglans sigillata (Juglandaceae), together with six known compounds. The structures of the new compounds were determined as 1,2,3,4‐tetrahydro‐7‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 1 ), (1S)‐1,2,3,4‐tetrahydro‐8‐hydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 2 ), and 1,2,3,4‐tetrahydro‐7,8‐dihydroxy‐4‐oxonaphthalen‐1‐yl 6‐O‐[(3,4,5‐trihydroxyphenyl)carbonyl]‐β‐D ‐glucopyranoside ( 3 ), respectively, on the basis of detailed spectroscopic analyses, and acidic and enzymatic hydrolysis. The antimicrobial activities of the isolated compounds 2, 4 , and 7 – 9 were evaluated.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

Semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane diterpene

Annonalide (3β,20‐epoxy‐3α,16‐dihydroxy‐15‐oxo‐7‐pimaren‐19,6β‐olide, C₂₀H₂₆O₆, 1 ) is the major (9βH)‐pimarane diterpene isolated from tubers of Cassimirella ampla, and it exhibits cytotoxic properties upon interaction with ctDNA. We have prepared new derivatives of 1 by modification of the (9βH)‐pimarane backbone and report here the semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane. Our approach was the reduction of the carbonyl groups of 1 with sodium borohydride, at positions C15 (no stereoselectivity) and C3 (stereoselective reduction), followed by rearrangement of the 6,19‐γ‐lactone ring into the six‐membered 19,20‐δ‐lactone ring in 4a (3β,6β,16‐trihydroxy‐7‐pimaren‐19,20β‐olide monohydrate, C₂₀H₃₀O₆·H₂O). The absolute structure of the new compound, 4a , was determined unambiguously with a Flack parameter x of −0.01 (11), supporting the stereochemistry assignment of 1 redetermined here. Besides the changes in the pattern of covalent bonds caused by reduction and lactone rearrangement, the conformation of one of the three fused cyclohexane rings is profoundly different in 4a , adopting a chair conformation instead of the boat shape found in 1 . Furthermore, the intramolecular hydrogen bond present in 1 is lost in new compound 4a , due to hydrogen bonding between the 3‐OH group and the solvent water molecule.     

Norbornane Mimics of Distorted β‐D‐Glucopyranosides – Inhibitors of β‐D‐Glucopyranosidases?

The racemic gluco‐configured norbornanes 4 and 16 were prepared and tested as inhibitors of β‐glucosidases. The known alcohol 5 was deprotected to provide the triol 6 . Silylation (→ 7 ), monobenzoylation (→ 8 / 9 ), and oxidation provided the regioisomeric ketones 10 and 11 . Reduction of 10 gave the desired endo‐alcohol 13 , albeit in low yield, while reduction of the isomeric ketone 11 provided mostly the altro‐configured endo‐alcohol 12 . The alcohol 13 was desilylated to 14 . Debenzoylation to 15 followed by hydrogenolytic deprotection gave the amino triol 4 that was reductively aminated to the benzylamine 16 . The amino triols 4 and 16 proved weak inhibitors of the β‐glucosidase from Caldocellum saccharolyticum ( 4 : IC₅₀ = 5.6 mm; 16 : IC₅₀ = 3.3 mm) and from sweet almonds ( 16 : IC₅₀ = 5.5 mm) . A comparison of 4 with the manno‐configured norbornane 3 shows that 3 is a better inhibitor of snail β‐mannosidase than 4 is of β‐glucosidases, in keeping with earlier results suggesting that these β‐glycosidases enforce a different conformational itinerary.     

New Prenylated Flavones from the Roots of Ficus Beecheyana

Two new prenylated flavanones, ficubee A and ficubee B, respectively, as 7,8‐(2,2‐dimethylpyrano)‐6‐prenyl‐5,3′,4′‐trihydroxyflavone and 6,7‐(2,2‐dimethylpyrano)‐8‐prenyl‐5,3′,4′‐trihydroxyflavone were isolated from the roots of Ficus beecheyana together with twelve known compounds: β‐sitosterol, 5‐stigmasten‐3β,7α‐diol, 5‐stigmasten‐3β,7β‐diol, 3β‐hydroxystigmast‐5‐en‐7‐one, 4‐hydroxybenzaldehyde, 4‐hydroxy‐3‐methoxybenzaldehyde, 1‐(4‐hydroxyphenyl)‐ethanone, 4‐hydroxy‐3‐methoxybenzoic acid, 4‐hydroxy‐cinnamic acid, seseline, xanthyletin, and psoralene. The structures of these secondary metabolites were determined by spectroscopic means and in comparison with published data.     

具有β-(1→6)-半乳吡喃糖骨架和α-L-(1→3)-阿拉伯呋喃糖侧链的阿拉伯半乳寡糖的简易合成

4-Methoxyphenyl glycoside of β-D-Galp-(1→6)-[α-L-Araf-(1→3)-]β-D-Galp-(1→6)-β-D-Galp-(1→6)-{β-D-Galp-(1→6)-[α-L-Araf-(1→3)-]β-D-Galp-(1→6)-β-D-Galp-(1→6)-}2β-D-Galp-(1→6)-[α-L-Araf-(1→)3)-]β-D-Galp-(1→)6)-β-D-Galp was synthesized with 2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (1), 6-O-acetyl-2,3,4-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (11), 4-methoxyphenyl 3-O-allyl-2,4-tri-O-benzoyl-β-D-galactopyranoside (2),isopropyl 3-O-allyl-2,4-tri-O-benzoyl--thio-β-D-galactopyranoside (12),4-methoxyphenyl 2,3,4-tri-O-benzoyl-β-D-galactopyranoside (5), and 2,3,5-tri-O-benzoyl-α-L-arabinofuranosyl trichloroacetimidate (8) as the key synthons.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Xanthone O‐Glycosides from the Roots of Pteris Multifida

Two new xanthone glycosides and six known compounds were isolated from the roots of Pteris multifida. Based on spectroscopic and chemical methods, the structures of the new compounds were elucidated as 1‐hydroxy‐4,7‐dimethoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 1 ), and 1,3‐dihydroxy‐7‐methoxy‐8‐(3‐methyl‐2‐butenyl)‐6‐O‐α‐L‐rhamnopyranosyl‐(1 →2)‐[β‐D‐glucopyranosyl‐(1→3)]‐β‐D‐glucopyranosylxanthone ( 2 ), respectively.     

Solid‐state conformations of linear depsipeptide amides with an alternating sequence of α,α‐disubstituted α‐amino acid and α‐hydroxy acid

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α‐disubstituted α‐amino acid and an α‐hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)‐Pms‐Acp‐(S)‐Pms‐Acp‐(S)‐Pms‐Acp‐NMe₂ acetonitrile solvate, C₄₇H₅₈N₄O₉·C₂H₃N, ( 3b ), as well as in the related linear tetradepsipeptide amide (S)‐Pms‐Aib‐(S)‐Pms‐Aib‐NMe₂, C₂₈H₃₇N₃O₆, ( 5a ), the diastereoisomeric mixture (S,R)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂/(R,S)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂ (1:1), C₃₂H₄₁N₃O₆, ( 5b ), and (R,S)‐Mns‐Acp‐(S,R)‐Mns‐Acp‐NMe₂, C₃₀H₃₇N₃O₆, ( 5c ) (Pms is phenyllactic acid, Acp is 1‐aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β‐turn conformation in the solid state, which is stabilized by intramolecular N—H…O hydrogen bonds. Whereas β‐turns of type I (or I′) are formed in the cases of ( 3b ), ( 5a ) and ( 5b ), which contain phenyllactic acid, the torsion angles for ( 5c ), which incorporates mandelic acid, indicate a β‐turn in between type I and type III. Intermolecular N—H…O and O—H…O hydrogen bonds link the molecules of ( 3a ) and ( 5b ) into extended chains, and those of ( 5a ) and ( 5c ) into two‐dimensional networks.     

Iron‐Catalyzed Aminomethyloxygenative Cyclization of Hydroxy‐α‐diazoesters with N,O‐Aminals

A new and efficient cyclization reaction has been developed to synthesize cyclic α,α‐disubstituted β‐amino esters via iron‐catalyzed intramolecular aminomethyloxygenative cyclization of diazo compounds with N,O‐aminal under mild reaction conditions. A broad range of hydroxy‐α‐diazoesters with different substituents and various N,O‐aminals were compatible with this protocol, affording the corresponding α,α‐disubstituted β‐amino esters bearing a five‐ to eight‐membered oxacycle in good yields.     

Synthesis of Novel Bis(β‐cyclodextrin)s Linked with Glycol and Their Inclusion Complexation with Organic Dyes

Three novel bis(β‐cyclodextrin (CD))s with flexible glycol linkers, i.e., ethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 2 ), diethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 3 ), and triethylene glycol‐bridged bis(6‐hydroxy‐6‐deoxy‐β‐CD) ( 4 ) have been synthesized by the reaction of mono[6‐O‐(p‐toluenesulfonyl)]‐β‐CD with corresponding materials. The inclusion complexation behaviors of these compounds 2 – 4 with organic dyes; that is, acridine red (=N‐[(3Z)‐6‐(methylamino)‐3H‐xanthen‐3‐ylidene]methanaminium chloride; AR), neutral red (=N⁸,N⁸,3‐trimethylphenazine‐2,8‐diamine hydrochloride; NR), ammonium 8‐anilinonaphthalene‐1‐sulfonate (ANS), sodium 6‐(p‐toluidinyl)‐naphthalene‐2‐sulfonate (TNS), rhodamine B (RhB) and brilliant green (=N‐(4‐{[4‐(diethylamino)cyclohexa‐2,5‐dien‐1‐yl](phenyl)methyl}cyclohex‐2‐en‐1‐ylidene)‐N‐ethyl‐ethanaminium hydrogen sulfate; BG), have been investigated at 25° in phosphate buffer (pH 7.20) by ultraviolet, fluorescence, and 2D‐NMR spectroscopy. The results indicate that the two linked CD units may cooperatively bind a guest, and the molecular binding ability toward dye guests, especially bent ANS, T‐shaped RhB, and triangular BG, can be extended. This cooperative binding mode is confirmed by Job's experiments and 2D‐NMR investigations. Furthermore, the complex stability depends greatly on the linker length of these glycol‐bridged bis(β‐CD)s and the size and shape of guest. The higher binding ability and selectivity of dye molecules by bis(β‐CD)s 2 – 4 are discussed from the viewpoint of size/shape‐fit concept and multiple recognition mechanism.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

Sterols from the Stems of Momordica charantia

A new sterol, 5α,6α‐epoxy‐3β‐hydroxy‐(22E,24R)‐ergosta‐8,22‐dien‐7‐one ( 1 ), together with eight known sterols, 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7α‐diol ( 2 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7β‐diol ( 3 ), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8(14),22‐diene‐3β,7α‐diol ( 4 ), 3β‐hydroxy‐(22E,24R)‐ergosta‐5,8,22‐trien‐7‐one ( 5 ), ergosterol peroxide ( 6 ), clerosterol ( 7 ), decortinol ( 8 ), and decortinone ( 9 ), were isolated from the stems of Momordica charantia. Their structures were elucidated by mean of extensive spectroscopic methods, including ¹H, ¹³C, 2D‐NMR and HR‐EI‐MS, as well as comparison with the literature data. Compounds 1 , 4 , 5 , 8 , and 91 were not cytotoxic against the SK‐Hep 1 cell line.     

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

α‐Amino phosphonic acid derivatives are considered to be the most important structural analogues of α‐amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2‐addition reactions of α‐isothiocyanato phosphonate were developed. Through these processes, derivatives of β‐hydroxy‐α‐amino phosphonic acid and α,β‐diamino phosphonic acid, as well as highly functionalized phosphonate‐substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α‐phosphonic acid derivatives.     

Five Aromatics Bearing a 4‐O‐Methylglucose Unit from Cordyceps cicadae

Five new aromatics bearing a 4‐O‐methylglucose unit, namely 3‐methoxy‐1,4‐hydroquinone 1‐(4′‐O‐methyl‐β‐glucopyranoside) (=4‐hydroxy‐3‐methoxyphenyl 4‐O‐methyl‐β‐glucopyranoside; 1 ), 3‐methoxy‐1,4‐hydroquinone 4‐(4′‐O‐methyl‐β‐glucopyranoside) (=4‐hydroxy‐2‐methoxyphenyl 4‐O‐methyl‐β‐glucopyranoside; 2 ), vanillic acid 4‐(4′‐O‐methyl‐β‐glucopyranoside) (=3‐methoxy‐4‐[(O‐methyl‐β‐glucopyranosyl)oxy]benzoic acid; 3 ), 5‐methoxycinnamic acid 3‐O‐(4′‐O‐methyl‐β‐glucopyranoside) (=(2E)‐3‐{3‐methoxy‐5‐[(4‐O‐methyl‐β‐glucopyranosyl)oxy]phenyl}prop‐2‐enoic acid; 4 ), and naphthalene‐1,8‐diol 1,8‐bis(4′‐O‐methyl‐β‐glucopyranoside) (=naphthalene‐1,8‐diyl bis(4‐O‐methyl‐β‐glucopyranoside; 5 ), were isolated from the cultivated Cordyceps cicadae mycelia, together with thirteen known compounds. Their structures were determined by spectroscopic methods. The absolute configurations of the sugar units were not determined.     

Flavonol Glycosides with α‐Glucosidase Inhibitory Activities and New Flavone C‐Diosides from the Leaves of Machilus konishii

Seventeen flavonoids, five of which are flavone C‐diosides, 1 – 5 , were isolated from the BuOH‐ and AcOEt‐soluble fractions of the leaf extract of Machilus konishii. Among 1 – 5 , apigenin 6‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 2 ), apigenin 8‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 4 ), and apigenin 8‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 5 ) are new. Both 4 and 5 are present as rotamer pairs. The structures of the new compounds were elucidated on the basis of NMR‐spectroscopic analyses and MS data. In addition, the ¹H‐ and ¹³C‐NMR data of apigenin 6‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 3 ) were assigned for the first time. The isolated compounds were assayed against α‐glucosidase (type IV from Bacillus stearothermophilus). Kaempferol 3‐O‐(2‐β‐D ‐apiofuranosyl)‐α‐L ‐rhamnopyranoside ( 12 ) was found to possess the best inhibitory activity with an IC₅₀ value of 29.3 μM .     

Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.