Two new xeniolides from a Taiwanese Xenia soft coral

Chromatographic investigation of an extract of the octocoral Xenia umbellata afforded two new diterpenes, xenibelatols A (1) and B (2), in addition to three known xenicane diterpenes, 7,8-oxidoisoxeniolide (3), 9-hydroxyxeniolide F (4), and florlide C, and a cadinene sesquiterpene, xenitorin A (5). The structures were elucidated through spectroscopic analysis, especially 2D NMR.     

A New Alkaloid from the Roots of Aconitum carmichaeli Debx.

A new diterpene alkaloid, 12‐epi‐15‐O‐acetyl‐17‐benzoyl‐16‐hydroxy‐16,17‐dihydronapelline ( 1 ), along with nine known diterpene alkaloids including yunaconitine ( 2 ), neoline ( 3 ), mesaconitine ( 4 ), beiwutine ( 5 ), chasmanine ( 6 ), songorine ( 7 ), 12‐epi‐napelline ( 8 ), foresticine ( 9 ), and 15α‐hydroxyneoline ( 10 ) were isolated from the roots of Aconitum carmichaeli Debx. The structure of compound 1 was elucidated by comprehensive spectroscopic analysis.     

Comparison of racemic epi‐inosose and (−)‐epi‐inosose

The conversion of myo‐inositol to epi‐inositol can be achieved by the hydride reduction of an intermediate epi‐inosose derived from myo‐inositol. (−)‐epi‐Inosose, (I), crystallized in the monoclinic space group P2₁, with two independent molecules in the asymmetric unit [Hosomi et al. (2000). Acta Cryst. C 56 , e584–e585]. On the other hand, (2RS,3SR,5SR,6SR)‐epi‐inosose, C₆H₁₀O₆, (II), crystallized in the orthorhombic space group Pca2₁. Interestingly, the conformation of the molecules in the two structures is nearly the same, the only difference being the orientation of the C‐3 and C‐4 hydroxy H atoms. As a result, the molecular organization achieved mainly through strong O—H...O hydrogen bonding in the racemic and homochiral lattices is similar. The compound also follows Wallach's rule, in that the racemic crystals are denser than the optically active form.     

Taxane Diterpenoids from the Root Bark of Taiwanese Yew Taxus Mairei

Nineteen compounds including taxumairol R (1) , taxinine M (2) , taxacin (3) , paclitaxel (4) , 10‐deacetyltaxol A (5) , 10‐deacetyl‐7‐epi‐taxol (6) , 7‐epi‐taxol (7) , taxol C, 10‐deacetyltaxol C, 7β‐xylosyl‐10‐deacetyltaxol (8) , taxamairin A (9) , taxinine A, 14β‐hydroxytaxusin (10) , 5α‐hydroxy‐7β,9α,10β, 13α‐tetraacetoxy‐4(20), 11‐taxadiene, 1‐dehydroxybaccatin‐VI, 1β‐dehydroxybaccatin‐IV, baccatin IV, baccatin VI and ponasterone A have been isolated and identified from the root bark of Taxus mairei. Among them, compound 1 was a new taxoid and compounds 11 and 7β‐xylosyl‐10‐deacetyltaxol pentaacetate were new derivatives prepared from 14β‐hydroxytaxusin (10) and 8 , respectively. Their structures and assignment were established on the basis of 2D‐NMR analysis and chemical methods.     

Hyrtiosins A–E,Five New Scalarane Sesterterpenes from the South China Sea Sponge Hyrtios erecta

Five new scalarane sesterterpenes, hyrtiosins A–E ( 1 – 5 ), together with three previously reported sesterterpenes, 25‐dehydroxy‐12‐epi‐scalarin ( 6 ), 12‐epi‐scalarin ( 7 ) and heteronemin ( 9 ), were isolated from the South China Sea sponge Hyrtios erecta. Their structures were determined on the basis of extensive NMR studies and high‐resolution MS measurements.     

Structure elucidation of new fusarielins from Fusarium sp. and their antimicrobial activity

Three new fusarielins, 3‐epi‐fusarielin H ( 1 ), 3‐O‐methyl‐fusarielin H ( 2 ), and 3‐O‐methyl‐epi‐fusarielin H ( 3 ), were isolated from the fungus Fusarium sp. together with the known analogues, fusarielins F ( 4 ) and G ( 5 ). The structures of these compounds were elucidated by analysis of their ESI‐HRTOFMS, 1D and 2D NMR spectroscopic data. The new compounds exhibited weak antibacterial effect against Staphylococcus aureus.     

Three New ent‐Kaurane Diterpenoids from Siegesbeckia pubescens

Three new ent‐kaurane glucopyranosides, 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐isovaleryl‐β‐D ‐glucopyranosyl]‐4‐epi‐atractyligenin ( 1 ), 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐isovaleryl‐β‐D ‐glucopyranosyl]atractyligenin ( 2 ), and 2‐O‐[β‐D ‐apiofuranosyl‐(1→3)‐2‐O‐(3‐methylpentanoyl)‐β‐D ‐glucopyranosyl]‐4‐epi‐atractyligenin ( 3 ), along with 2‐O‐(2‐O‐isovaleryl‐β‐D ‐glucopyranosyl)‐4‐epi‐atractyligenin ( 4 ), were isolated for the first time from the aerial parts of Siegesbeckia pubescens. The structures were established by extensive spectroscopic analyses including 1D ‐ and 2D ‐NMR (HSQC, HMBC, and ROESY), and HR‐ESI‐MS, and by comparison with published data.     

C5–C10 Directly Bonded Tetrodotoxin Analogues: Possible Biosynthetic Precursors of Tetrodotoxin From Newts

The identification of novel tetrodotoxin (TTX, 1 ) analogues would significantly contribute to the elucidation of its biosynthetic pathway. In this study, the first C5–C10 directly bonded TTX analogues, 4,9‐anhydro‐10‐hemiketal‐5‐deoxyTTX ( 2 ) and 4,9‐anhydro‐8‐epi‐10‐hemiketal‐5,6,11‐trideoxyTTX ( 3 ), were found in the newt Cynops ensicauda popei by using a screening method involving HILIC‐LC–MS/MS focused on the fragment ions of TTX analogues, and their structures were elucidated by spectroscopic methods. Compound 2 was detected in a wide range of newt species, and the 2 and TTX contents of 22 newt specimens were correlated (r_s=0.88). Based on these results and its structural features, 2 was predicted to serve as a precursor of TTX that would be directly converted into 4,9‐anhydroTTX ( 4 ) by Baeyer–Villiger‐like oxidation or via 4,9‐anhydro‐5‐deoxyTTX formed by cleavage of the C5–C10 bond. The bicyclic carbon skeletons of 2 and 3 suggested a possible monoterpene origin for TTX.     

Diketopiperazine Alkaloids Produced by the Endophytic Fungus Aspergillus fumigatus from the Stem of Erythrophloeum fordii Oliv.

Four new diketopiperazine alkaloids, rel‐(8R)‐9‐hydroxy‐8‐methoxy‐18‐epi‐fumitremorgin C ( 1 ), rel‐(8S)‐19,20‐dihydro‐9,20‐dihydroxy‐8‐methoxy‐9,18‐di‐epi‐fumitremorgin C ( 2 ), rel‐(8S,19S)‐19,20‐dihydro‐9,19,20‐trihydroxy‐8‐methoxy‐9‐epi‐fumitremorgin C ( 3 ), and (3S,8S,9S,18S)‐8,9‐dihydroxyspirotryprostatin A ( 4 ), together with the eight known compounds 5 – 12 , were isolated from the endophytic fungus Aspergillus fumigatus. The structures of the new compounds were determined by extensive spectroscopic methods including HR‐ESI‐MS, NMR, and CD experiments. Compound 12 showed weak inhibitory activity in vitro against the release of β‐glucuronidase in rat polymorphonuclear leukocytes induced by the platelet‐activating factor. None of the twelve compounds exhibited detectable cytotoxic activities toward five human tumor cell lines (HCT‐8, Bel‐7402, BGC‐823, A549, and A2780) in the MTT assay.     

Sesquiterpenoids from Senecio argunensis

Investigation of unpolar extracts from the aerial parts of Senecio argunensis afforded two new sesquiterpenoids, 1β‐hydroxyeudesma‐4,11‐dien‐15‐al ( 1 ) and 4(15)‐cadinene‐5α,10α‐diol, ( 2 ) as well as six known compounds, 3 – 8 . The structures of all isolates were elucidated on the basis of extensive analyses of spectroscopic data and comparison with literature data.     

Cadinene Derivatives from Eupatorium adenophorum

A new norsesquiterpene named eupatorone (= (4S,4aR,6R)‐1‐acetyl‐6‐(acetyloxy)‐4,4a,5,6‐tetrahydro‐4,7‐dimethylnaphthalen‐2(3H)‐one; 1 ) and a new sesquiterpene derivative named 2‐deoxo‐2‐(acetyloxy)‐9‐oxoageraphorone (= (1R,4S,4aR,6R,8aS)‐6‐(acetyloxy)‐3,4,4a,5,6,8a‐hexahydro‐4,7‐dimethyl‐1‐(1‐methylethyl)naphthalen‐2(1H)‐one; 2 ), together with the five known cadinene derivatives 3 – 7 were isolated from the flower of Eupatorium adenophorum (Spreng. ). Their structures were established by extensive NMR experiments, including 1D and 2D NMR.     

gem‐Dihalocyclopropanes as Building Blocks in Natural‐Product Synthesis: Enantioselective Total Syntheses of ent‐Erythramine and 3‐epi‐Erythramine

ent‐Erythramine ((?)‐ 1 ), the enantiomer of the alkaloid erythramine, was prepared in 15 steps from known compounds. The first of three pivotal bond‐forming steps in the synthesis was a Suzuki–Miyaura cross‐coupling reaction of the starting materials to give a bis‐silyl ether. The second involved silver(I)‐induced electrocyclic ring opening of the gem‐dichlorocyclopropane formed in the next step and trapping of the ensuing π‐allyl cation by the tethered nitrogen atom to give, following cleavage of the allyloxycarbonyl protecting group, an approximately 5:6 mixture of the chromatographically separable diastereoisomeric spirocyclic products. In the third critical bond‐forming reaction, the iodide formed from one of the diastereoisomers underwent a radical‐addition/elimination reaction sequence that led to (?)‐ 1 in 89 % yield. The application of the same sequence of transformations to the other diastereoisomer afforded 3‐epi‐(+)‐erythramine (3‐epi‐(+)‐ 1 ).     

Sesquiterpene Coumarins from Ferula Foetida

A thorough investigation of the ethyl acetate soluble fraction from a methanol extract of the resin of Ferula foetida has resulted in the isolation of a new sesquiterpene coumarin namely epi‐conferdione ( 1 ), along with four known compounds, colladonin ( 2 ), karatavicinol ( 3 ), 8‐acetoxy‐5‐hydroxyumbelliprenin ( 4 ), and asacoumarin ( 5 ). These structures were elucidated on the basis of extensive spectroscopic techniques, including 1D and 2D NMR spectroscopy. The absolute configuration of the new compound was established by circular dichroism (CD).     

Synthesis and Biological Activities of Novel Seleno epi-Daunomycin Derivatives

Abstract

3′-[2-(Selenoaryl)acetamido]epi-daunomycin derivatives 2a–d and 4′-[2-(selenoaryl)acetoxy]-N-(trifluoroacetyl)epi-daunomycin derivatives 4a–e were synthesized from epi-daunomycin 1d and N-trifluoroacetyl epi-daunomycin 3, respectively. These new compounds were assayed against human stomach cancer SGC-7901 and human leukaemia HL60.     

Collective Synthesis and Biological Evaluation of Tryptophan‐Based Dimeric Diketopiperazine Alkaloids

A concise two one‐pot synthesis of WIN 64821, eurocristatine, 15,15′‐bis‐epi‐eurocristatine, ditryptophenaline, ditryptoleucine A, WIN 64745, cristatumin C, asperdimin, naseseazine A, and naseseazine B is detailed, based on a unique bioinspired dimerization reaction of tryptophan derivatives in aqueous acidic solution and a one‐pot procedure for the construction of diketopiperazine rings. Total yields of these alkaloid syntheses were from 10 up to 27 %. In addition, 1′‐(2‐phenylethylene)‐ditryptophenaline was synthesized by using three one‐pot operations. The studies detailed herein provided synthesized natural products for inhibitory activities of ubiquitin‐specific protease 7 (USP7) and foam cell formation in macrophages. The newly listed biological evaluation for tryptophan‐based dimeric diketopiperazine alkaloids discovered 15,15′‐bis‐epi‐eurocristatine, 1′‐(2‐phenylethylene)‐ditryptophenaline, and WIN 64745 as new drug candidates.     

Enantioselective Synthesis of Arene cis‐Dihydrodiols from 2‐Pyrones

An enantioselective chemical synthesis of arene cis‐dihydrodiols has been realized from 2‐pyrones through sequential ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 2‐pyrones and retro‐Diels–Alder extrusion of CO₂. By using this strategy, a series of substituted arene cis‐dihydrodiols can be obtained efficiently with high enantioselectivity (>99 % ee in many cases). Based on this strategy, efficient and concise asymmetric total syntheses of (+)‐MK7607 and 1‐epi‐(+)‐MK7607 were accomplished.     

Unified Total Synthesis of 3‐epi‐Ryanodol,Cinnzeylanol, Cinncassiols A and B,and Structural Revision of Natural Ryanodol and Cinnacasol

Ryanodane diterpenoids structurally share an extremely complex fused ring system, but differ in the substitution patterns of the hydroxy groups. Since these congeners exhibit various biologically important functions, their efficient chemical constructions have been greatly anticipated. We previously accomplished the total synthesis of ryanodine ( 1 ) using pentacycle 8 as the advanced intermediate. Here, we report the unified total syntheses of four distinct diterpenoids, 3‐epi‐ryanodol ( 3 ), cinnzeylanol ( 4 ), cinncassiols B ( 5 ), and A ( 6 ), from 8 , all within 10 steps. A series of highly optimized chemo‐ and stereoselective reactions and protecting‐group manipulations enabled assembly of the densely oxygenated structures of 3 – 6 . Furthermore, the present synthetic studies established the C13S stereochemisty of 5 – 7 and revised the proposed structures of natural ryanodol ( 2 ) and cinnacasol ( 7 ) to be those of 3 and 6 , respectively.     

Unified Total Synthesis of 3‐epi‐Ryanodol,Cinnzeylanol, Cinncassiols A and B,and Structural Revision of Natural Ryanodol and Cinnacasol

Ryanodane diterpenoids structurally share an extremely complex fused ring system, but differ in the substitution patterns of the hydroxy groups. Since these congeners exhibit various biologically important functions, their efficient chemical constructions have been greatly anticipated. We previously accomplished the total synthesis of ryanodine ( 1 ) using pentacycle 8 as the advanced intermediate. Here, we report the unified total syntheses of four distinct diterpenoids, 3‐epi‐ryanodol ( 3 ), cinnzeylanol ( 4 ), cinncassiols B ( 5 ), and A ( 6 ), from 8 , all within 10 steps. A series of highly optimized chemo‐ and stereoselective reactions and protecting‐group manipulations enabled assembly of the densely oxygenated structures of 3 – 6 . Furthermore, the present synthetic studies established the C13S stereochemisty of 5 – 7 and revised the proposed structures of natural ryanodol ( 2 ) and cinnacasol ( 7 ) to be those of 3 and 6 , respectively.     

Rare C25 Steroids Produced by Penicillium chrysogenum P1X,a Fungal Endophyte of Huperzia serrata

Three new metabolites, norcyclocitrinol A ( 1 ), erythro‐11α‐hydroxyneocyclocitrinol ( 2 ), and pesudocyclocitrinol A ( 3 ), along with six known analogs, i.e., neocyclocitrinols A–D ( 4 – 7 , resp.), cyclocitrinol ( 8 ), and 24‐epicyclocitrinol ( 9 ), were isolated and identified from the culture broth of Penicillium chrysogenum P1X, a fungal endophyte of Huperzia serrata. Compounds 1 – 9 were identified by spectroscopic methods to share the same C₂₅‐steroid skeleton featuring an unusual bicyclo[4.4.1] A/B ring system. In particular, 1 represents the first example of a C₂₅ steroid with a bisnor C‐atom side chain. All compounds were evaluated for their cytotoxic activities against HeLa and HepG2 cell lines. However, none of them exhibited a significant cytotoxicity at a concentration of 20 μM .     

Synthesis and NMR characteristics of N‐acetyl‐4‐nitro,N‐acetyl‐5‐nitro,N‐acetyl‐6‐nitro and N‐acetyl‐7‐nitrotryptophan methyl esters

N‐acetyl‐4‐nitrotryptophan methyl ester (2), N‐acetyl‐5‐nitrotryptophan methyl ester (3), N‐acetyl‐6‐nitrotryptophan methyl ester (4) and N‐acetyl‐7‐nitrotryptophan methyl ester (5) were synthesized through a modified malonic ester reaction of the appropriate nitrogramine analogs followed by methylation with BF₃‐methanol. Assignments of the ¹H and ¹³C NMR chemical shifts were made using a combination of ¹H–¹H COSY, ¹H–¹³C HETCOR and ¹H–¹³C selective INEPT experiments. Copyright © 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd