Total Synthesis of Siomycin A: Construction of Synthetic Segments

The five practical segments for the total synthesis of siomycin A, that is, the dehydropiperidine segment A ( 5 ), the pentapeptide segment B ( 3 ), the dihydroquinoline segment C ( 6 ), and the β‐phenylselenoalanine dipeptide segments D ( 7 ) and E ( 4 ), were synthesized. Segment A ( 5 ) was constructed by the coupling of the azomethine ylide and the chiral sulfinimine, followed by the stereoselective reduction of the six‐membered imine function. Segment B ( 3 ) was synthesized by the phenylselenylation of the β‐lactone, stereoselective vinylzinc addition to the chiral sulfinimine, and oxazoline–thioamide conversion. Segment C ( 6 ) was prepared by the one‐pot olefination of the tetrahydroquinoline N‐oxide using triflic anhydride and triethylamine, stereoselective reduction of the methyl ketone function, and regioselective Yb(OTf)₃‐catalyzed epoxide opening by the amino group. Segments D ( 7 ) and E ( 4 ) were synthesized by coupling of the properly protected β‐phenylselenoalanines.     

Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594

A highly convergent approach was developed to achieve the first asymmetric and scalable total synthesis of FD‐594, a complex polycyclic xanthone natural product from Streptomyces sp. TA‐0256, in a longest linear sequence (LLS) of 20 steps. The trans‐9,10‐dihydrophenanthrene‐9,10‐diol fragment (B‐C‐D ring) was generated through a new strategy involving asymmetric dihydroxylation followed by Cu‐mediated oxidative cyclization. Late‐stage stereoselective glycosylation assembled the angular hexacyclic framework with a β‐linked 2,6‐dideoxy trisaccharide fragment.     

丁酸氯维地平降解杂质的合成

以4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸(2-氰基乙基)（甲基）酯(5)为起始原料,合成了丁酸氯维地平的5种降解杂质：4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯(A), 4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3-吡啶羧酸甲酯(B), 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸单甲酯(C), 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸（丁酰氧基甲基）（甲基）酯(D)和4-(2,3-二氯苯基)-2,6-二甲基-3-吡啶羧酸甲酯(E)。其中A由5水解制得;B由A脱羧制得;C由5氧化后再经水解制得;D由C和丁酸氯甲酯缩合制得;E由C脱羧制得,化合物结构经¹H NMR和MS（ESI）确证。     

Asymmetric Formal Synthesis of Azadirachtin

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley’s synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right‐hand segment starting from the known 5‐hydroxymethyl‐2‐cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α‐oxidation of the six‐membered lactone followed by methanolysis.     

Glycopolymeric inhibitors of β‐glucuronidase I. Synthesis and polymerization of styrene derivatives having pendant D‐glucaric moieties

Two kinds of novel vinyl monomers having D ‐glucaric moieties leading to a new type of glycopolymeric inhibitors of β‐glucuronidase, N‐p‐vinylbenzyl‐6‐D ‐glucaramide (6 ) and potassium N‐p‐vinylbenzyl‐6‐D ‐glucaramid‐1‐ate (8 ), were synthesized by the reaction of D ‐glucaro‐6,3‐lactone (3 ) with p‐vinylbenzylamine (5 ) with no catalyst, and the subsequent treatment of the reaction mixture with acetic anhydride and potassium hydroxide aqueous solution, respectively. The radical copolymerization of 8 with acrylamide in various feed ratios at 60°C in 0.1 N potassium chloride aqueous solution gave water‐soluble copolymers (9 ) composed of a synthetic polymeric main chain and many pendant D ‐glucaric chains. The resulting glycopolymers (9 ) were found to inhibit the activity of β‐glucuronidase strongly through a model reaction with p‐nitrophenyl β‐D ‐glucuronide (10 ) in acetic buffer solution (pH 4.7). © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 303–312, 1999     

Total Synthesis of Crotophorbolone

The complex ABC‐tricyclic structure of crotophorbolone, a derivative of the tigliane diterpenoids, was assembled by coupling of simple fragments. The six‐membered C‐ring fragment, having five contiguous stereocenters, was stereoselectively constructed from (R)‐carvone. After attachment of the five‐membered A‐ring through the π‐allyl Stille coupling reaction, the α‐alkoxy bridgehead radical reaction effected the endo‐cyclization of the seven‐membered B‐ring by forming the sterically congested bond at C9 and C10 stereospecifically and stereoselectively, respectively. Finally, the functional groups on the 5/7/6‐membered ring system were manipulated by rhodium‐catalyzed C2 olefin isomerization, C13 decarboxylative oxidation, and C4 hydroxylation, thus completing the first total synthesis of crotophorbolone.     

Gramicidin S Derivatives Containing cis‐ and trans‐Morpholine Amino Acids (MAAs) as Turn Mimetics

The cyclic decapeptide gramicidin S (GS) was used as a model for the evaluation of four turn mimetics. For this purpose, one of the D ‐Phe‐Pro two‐residue turn motifs in the rigid cyclic β‐hairpin structure of GS was replaced with morpholine amino acids (MAA 2 – 5 ), differing in stereochemistry and length of the side‐chain. The conformational properties of the thus obtained GS analogues ( 6 – 9 ) was assessed by using NMR spectroscopy and X‐ray crystallography, and correlated with their biological properties (antimicrobial and hemolytic activity). We show that compound 8 , containing the dipeptide isostere trans‐MAA 4 , has an apparent high structural resemblance with GS and that its antibacterial activity against a panel of Gram positive and ‐negative bacterial strains is better than the derivatives 6 , 7 and 9 .     

Benzoannulation of Quinones by a Cycloaddition‐Fragmentation Approach. A Simple Synthesis of Methoxycarbonyl‐Substituted Polyacenoquinones

The cycloadducts 2A‐5A obtained from the Diels‐Alder cycloadditions of 1,2,3,4‐tetrachloro‐4,5‐dimethoxycyclopentadiene ( 1 ) with p‐benzoquinone ( 2 ), 1,4‐naphthoquinone ( 3 ), 1,4‐anthraquinone ( 4 ), and 2,3‐dicyano‐1,4‐benzoquinone ( 5 ) were subjected to the reaction with triethylamine in dichloromethane at room temperature. Cycloadducts 2A and 5A enolized to give the corresponding hydroquinones 2B and 5B , which were oxidized with DDQ to afford naphthoquinone ester 2D and anthraquinone ester 5D , respectively. In the cases of cycloadducts 3A and 4A , the enolization occurred concurrently with oxidation and fragmentation to produce directly the polyacenoquinone esters 3D and 4D , respectively. Under the same reaction condition, the unsymmetrical cycloadduct 6A derived from naphthoquinone ester 2D and 1 yielded isomeric polyacenoquinone esters 6Da and 6Db in a ratio of about 8:1.     

Five New Quassinoids from the Bark of Picrasma quassioides

Five new quassinoids, named picraqualides A–E ( 1 – 5 ), together with eleven known ones, nigakilactone E ( 6 ), nigakilactone F ( 7 ), kusulactone ( 8 ), javanicin U ( 9 ), 12‐norquassin ( 10 ), quassin ( 11 ), 2,3‐didehydropicrasin B ( 12 ), nigakilactone B ( 13 ), nigakilactone C ( 14 ), picrasin B ( 15 ), and simalikalacton C ( 16 ), were isolated from the EtOH extract of the bark of Picrasma quassioides (D. Don ) Benn . Their structures were determined mainly by spectroscopic methods, especially by 2D‐NMR techniques and circular dichroism (CD). Some empirical rules were summarized on the basis of ¹³C‐NMR spectral analysis to distinguish between OH (or Ac) groups attached at C(11) vs. C(13).     

Total Synthesis of the Bicyclic Depsipeptide HDAC Inhibitors Spiruchostatins A and B, 5′′‐epi‐Spiruchostatin B,FK228 (FR901228) and Preliminary Evaluation of Their Biological Activity

The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins A and B, 5′′‐epi‐spiruchostatin B and FK228 were efficiently synthesized in a convergent and unified manner. The synthetic method involved the following crucial steps: i) a Julia–Kocienski olefination of a 1,3‐propanediol‐derived sulfone and a L ‐ or D ‐malic acid‐derived aldehyde to access the most synthetically challenging unit, (3S or 3R,4E)‐3‐hydroxy‐7‐mercaptohept‐4‐enoic acid, present in a D ‐alanine‐ or D ‐valine‐containing segment; ii) a condensation of a D ‐valine‐D ‐cysteine‐ or D ‐allo‐isoleucine‐D ‐cysteine‐containing segment with a D ‐alanine‐ or D ‐valine‐containing segment to directly assemble the corresponding seco‐acids; and iii) a macrocyclization of a seco‐acid using the Shiina method or the Mitsunobu method to construct the requisite 15‐ or 16‐membered macrolactone. The present synthesis has established the C5′′ stereochemistry of spiruchostatin B. In addition, HDAC inhibitory assay and the cell‐growth inhibition analysis of the synthesized depsipeptides determined the order of their potency and revealed some novel aspects of structure–activity relationships. It was also found that unnatural 5′′‐epi‐spiruchostatin B shows extremely high selectivity (ca. 1600‐fold) for class I HDAC1 (IC₅₀=2.4 nM ) over class II HDAC6 (IC₅₀=3900 nM ) with potent cell‐growth‐inhibitory activity at nanomolar levels of IC₅₀ values.     

Total synthesis of leustroducsin B

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.     

Synthesis of some new fused coumarin derivatives

2-Hydrazino-4-hydroxy-5H- [1] -benzopyrano- [ 4,3-d ] -pyrim-idin-5-one (3) was prepared via condensation of 2 with hy-drazine hydrate. Treatment of 3 with methylene chloride, ethyl chloroformate, ethyl chloroacetate and benzaldehyde yielded the corresponding 2 - ( substituted ) hydrazino - 4 -hydro-xy-5H-[1]-benzopyrano-[4, 3-d]-pyrimidin-5-one (4, 5, 6, and 10), followed by cyclization of 4, 5 and 6 with dimethyl fonnamide and fused sodium acetate under reflux, while compound 10 was cyclized with bromine and sodium acetate in acetic acid. Compound 3 reacted with β-(toloyl) acrylic acid, ethyl α-cyano-p-methoxytinnamate, diethyl mal-onate and acetyl chloride affording the corresponding 2-(substituted) hydrazino-4-hydroxy-5H-[1]-benzopyrano-[4, 3-d]-pyrimidin-5-one (12, 13, 14, 15 and 16).     

A New p‐Terphenyl Derivative from the Mushroom Thelephora vialis

One novel p‐terphenyl compound, named vialisyl A ( 1 ), was isolated from the fruiting bodies of Thelephora vialis, together with six known compounds, ganbajunin B ( 2 ), phenylacetic acid ( 3 ), a mixture of ganbajunins D ( 4 ) and E ( 5 ), and vialinins A ( 6 ) and B ( 7 ). Their structures were established by extensive analysis of spectroscopic data (including ¹H‐ and ¹³C‐NMR, HSQC, HMBC, 2D‐INADEQUATE) as well as by comparison with literature reports.     

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.     

Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2‐deoxy β‐C‐arylglycoside, and a late‐stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2‐deoxy sugar subunits for structure and activity relationship studies.     

Verpacamides A-D, a sequence of C11N5 diketopiperazines relating cyclo(Pro-Pro) to cyclo(Pro-Arg), from the marine sponge Axinella vaceleti: possible biogenetic precursors of pyrrole-2-aminoimidazole alkaloids

[reaction: see text] Four C(11)N(5) diketopiperazine metabolites named verpacamides A (6), B (7), C (8), and D (9) consisting of a proline-arginine dipeptide skeleton have been isolated from the marine sponge Axinella vaceleti. Verpacamides A-D are a sequence of metabolites showing the transformation of proline and arginine into the oxidized guanidinyl-cyclo(Pro-Pro) 8 and 9. Compounds 6-9 are structurally and chemically related to C(11)N(5) pyrrole-2-aminoimidazole metabolites also isolated from the Axinellidae and Agelasidae families of sponges and exemplified by dispacamide A (4) and dibromophakellin (10).     

Physical properties of diblock methylcellulose derivatives with regioselective functionalization patterns: First direct evidence that a sequence of 2,3,6‐tri‐O‐methyl‐glucopyranosyl units causes thermoreversible gelation of methylcellulose

This article describes detailed structure‐property relationships of 5 regioselectively methylated celluloses and 10 diblock cellulose derivatives with regioselective functionalization patterns: methyl 2,3,6‐tri‐O‐ ( 1 , 236MC), methyl 2,3‐di‐O‐ ( 2 , 23MC), methyl 2,6‐di‐O‐ ( 3 , 26MC), methyl 3‐O‐ ( 4 , 3MC), methyl 6‐O‐methyl‐cellulosides ( 5 , 6MC), methyl β‐D‐glucopyranosyl‐(1→4)‐2,3,6‐tri‐O‐methyl‐ ( 6 , G‐236MC), methyl β‐D‐glucopyranosyl‐(1→4)‐2,3‐di‐O‐methyl‐ ( 7 , G‐23MC), methyl β‐D‐glucopyranosyl‐(1→4)‐2,6‐di‐O‐methyl‐ ( 8 , G‐26MC), methyl β‐D‐glucopyranosyl‐(1→4)‐3‐O‐methyl‐ ( 9 , G‐3MC), methyl β‐D‐glucopyranosyl‐(1→4)‐6‐O‐methyl‐ ( 10 , G‐6MC), methyl β‐D‐glucopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→4)‐2,3,6‐tri‐O‐methyl‐ ( 11 , GG‐236MC), methyl β‐D‐glucopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→4)‐2,3‐di‐O‐methyl‐ ( 12 , GG‐23MC), methyl β‐D‐glucopy‐ranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→4)‐2,6‐di‐O‐methyl‐ ( 13 , GG‐26MC), methyl β‐D‐glucopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→4)‐3‐O‐methyl‐ ( 14 , GG‐3MC), and methyl β‐D‐glucopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→4)‐6‐O‐methyl‐cellulosides ( 15 , GG‐6MC). Surface tension, differential scanning calorimetry, fluorescence, and dynamic light scattering measurements of aqueous solutions of compounds 1 – 15 revealed that there was no relationship between aggregation behaviors and gel formation, gelation occurred only when the hydrophobic environments formed by hydrophobic interactions between the sequences of 2,3,6‐tri‐O‐methyl‐glucopyranosyl units upon heating. The diblock structure consisting of cellobiosyl block and approx. ten 2,3,6‐tri‐O‐methyl‐glucopyranosyl units was of crucial importance for thermoreversible gelation of methylcellulose. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1539–1546, 2011     

Chemical Constituents from the Roots of Patrinia Rupestris

Phytochemical investigation of the roots of Patrinia rupestris afforded a new triterpenoid patrirupin A ( 1 ) and a new iridoid patrirupin B ( 2 ), as well as three known triterpenoids: 3‐oxo‐olean‐12‐en‐28‐oic acid ( 3 ), ursolic acid ( 4 ), α‐amyrin ( 5 ), three known iridoids: isovaltratum ( 6 ), 11‐ethoxyviburtinal ( 7 ), homobaldrinal ( 8 ), five known steroids: ergosterol ( 9 ), ergost‐6,22‐diene‐3β,5α,8α‐triol ( 10 ), 6‐hydroxenone ( 11 ), β‐sitosterol ( 12 ), daucosterol ( 13 ), and two known flavones: 1‐hydroxy‐5‐methoxy xanthen‐9‐one ( 14 ), 3′,4′,5,7‐tetrahydroxyflavanone ( 15 ). The new compounds were characterized by means of spectroscopic methods including UV, IR, 1D, 2D NMR and HRESIMS, and the known ones were established on the basis of comparing their NMR data with those of the corresponding compounds in the literature.     

Convergent solid phase peptide synthesis. II. Synthesis of the 1–6 apamin protected segment on a NBB-resin. Synthesis of apamin

The article deals with the use of the NBB-resin for synthesis of protected segments followed by solid phase segment condenstaion. Solid phse synthesis on a NBB-resin of the segment 1–6 of apamin yielded either the (1–6) apamin-OH segment after photolysis or (1–6) apamin-NH-NH₂ after hydrazinolysis. The two protected segments were purified on Sephaex LH-20 followed by Bio-Beads S-X1 chromatography and respectively coupled onto a resin on which the 7–18 sequence of apamin was assembled stepwise with the standard solid phase procedure. On a portion of the resin, stepwise synthesis was continued to complete apamin. After HF treatment, deprotection of the cysteines, formation of the disulfide bonds and purification, biologically active apamin was obtained in the three cases.     

Synthesis of new side‐group liquid crystalline block copolymers by living anionic polymerization

A new series of AB liquid crystalline (lc) block copolymers was synthesized via living anionic copolymerization of styrene as segment A and 6‐[4‐(4‐cyanophenylazo)phenoxy]hexyl methacrylate ( 1 ) as segment B. The copolymers were successfully prepared in quantitative yields and with narrow molar mass distributions. The number‐average molar mass of the segments was varied well‐defined. The polystyrene block ranged from 3 500 to 7 400 g/mol. The content of the B segment ranged from 1 to 54 wt.‐%. Thermotropic phases were detected by differential scanning calorimetry (DSC) for block copolymers with an lc segment of more than 30 wt.‐%.