Synthesis of indole analogues of the anti-Helicobacter pylori compounds CJ-13,015, CJ-13,102, CJ-13,104 and CJ-13,108

Racemic syntheses of indole analogues of four phthalide-containing anti-Helicobacter pylori agents CJ-13,015, CJ-13,102, CJ-13,104 and CJ-13,108 are reported via manipulation of a common intermediate. This intermediate was formed by the N-alkylation of 4,6-dimethoxyindole with a long chain bromide followed by further chain extension. Oxidation, acetylation, or Barton-McCombie deoxygenation of the intermediate followed by Wacker oxidation afforded three analogues whilst further reduction of one analogue afforded the final analogue.     

Synthesis of the phthalide-containing anti-Helicobacter pylori agents CJ-13,015, CJ-13,102, CJ-13,103, CJ-13,104 and CJ-13,108

Flexible racemic syntheses of the phthalide-containing antibiotics CJ-13,015, CJ-13,102, CJ-13,103, CJ-13,104 and CJ-13,108 that inhibit Helicobacter pylori have been carried out in a convergent fashion by Wittig coupling of a phthalide-containing aldehyde fragment with an appropriate phosphorous ylide.     

Synthesis of heliannane skeletons. Facile preparation of (±)-heliannuol D

Heliannuol D is a natural product with a 7,10-heliannane skeleton, isolated from Helianthus annuus. It has been synthesized in eight steps, in good yield, using a new biomimetic method. Key steps were a Fries rearrangement, a Grignard reaction and, finally, a base catalyzed cyclization.     

Synthesis of N-linked glycan derived from Gram-negative bacterium, Campylobacter jejuni

Recent research has revealed the presence of asparagine (Asn)-linked (N-linked) glycoproteins in certain prokaryotes. In this paper, we describe the chemical synthesis of a novel N-glycan derived from Campylobacter jejuni, a heptasaccharide composed of Asn-linked bacillosamine (Bac), repeating GalNAc, and branching Glc, namely GalNAc-α(1,4)-GalNAc-α(1,4)-[Glc-β(1,3)-]GalNAc-α(1,4)-GalNAc-α(1,4)-GalNAc-α(1,3)-Bac. The synthesis started from a Bac-acceptor, which was consecutively glycosylated with 4-O-pentafluoropropionyl (PFP) protected donors to give heptasaccharide. Reduction of azide groups was followed by debenzylation to complete the synthesis of the target oligosaccharide.     

A concise synthesis of (±)-pseudodeflectusin, an antitumor isochroman derivative isolated from Aspergillus sp.

A novel and concise synthesis of (±)-pseudodeflectusin (1), an antitumor isochroman derivative isolated from the culture broth of Aspergillus pseudodeflectus, was accomplished by starting from 4-(tert-butyldimethylsilyloxy)-1-pentyne (3) and diethyl 3-oxopentanedicarboxylate (5).     

Synthesis of (±)-5′-methoxyhydnocarpin-D, an inhibitor of the Staphylococcus aureus multidrug resistance pump

The total synthesis of regioisomerically pure (±)-5′-methoxyhydnocarpin-D (6) from commercially available vanillin (7), methyl gallate (9) and 2′,4′,6′-trihydroxyaceophenone (10) is achieved.     

Efficient construction of novel α-keto spiro ketal and the total synthesis of (±)-terreinol

The first total synthesis of (±)-terreinol is described. An intramolecular Pd(II)-catalyzed cycloisomerization of a 2-(1′-alkynyl)benzyl alcohol via an apparent 6-endo diagonal pathway led to the 1H-isochromene ring system, which was further converted to the desired spiro ketal via an iodine-mediated intramolecular spiro-cyclization.     

First synthesis of (±)-sorgomol, the germination stimulant for root parasitic weeds isolated from Sorghum bicolor

Sorgomol, isolated from Sorghum bicolor, is the germination stimulant for seeds of root parasitic weeds. The first synthesis of (±)-sorgomol has been achieved by starting from ethyl 2-oxocyclohexanecarboxylate.     

Synthetic studies on basidifferquinones: the first synthesis of (±)-basidifferquinone C

Basidifferquinones, isolated from Streptomyces sp., are potent inducers for fruiting-body formation of a basidiomycete Polyporus arcularius. Construction of the basic framework of basidifferquinones and the first synthesis of (±)-basidifferquinone C were accomplished by starting from 3,5-dihydroxy-2-naphthoic acid.     

Total synthesis of (±)-hyrtiazepine

The total synthesis of the azepinoindole alkaloid, (±)-hyrtiazepine, was achieved. Construction of the azepinoindole core structure was carried out by C-4 selective α-hydroxyalkylation of 5-hydroxyindole, introduction of serine at C-3 of the indole moiety, and intramolecular imination.     

Total synthesis of (±)-brazilin and formal synthesis of (±)-brazilein, (±)-brazilide A using m-CPBA

Total synthesis of (±)-brazilin has been accomplished. m-CPBA epoxidation of allyl alcohol 10 and epoxy opening reaction mediated by m-chlorobenzoic acid, formed in situ as a byproduct, gave advanced intermediate diol 14. O-alkylation and cyclization gave phenol 6 which enabled the formal synthesis of (±)-brazilein and (±)-brazilide A.     

Synthesis of the Lewis b pentasaccharide and a HSA-conjugate thereof

Helicobacter pylori, a gastric pathogen, binds to various blood group antigens, including the Lewis types, present in the gastric tissue and a relation between the presentation of the ligands and the overall strength of binding has been assumed. Synthetic Lewis b tetra- and hexasaccharide conjugates are available but not the analogous pentasaccharide. An efficient synthesis of the amino spacer equipped Lewis b pentasaccharide, 3-aminopropyl α-l-fucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)-[α-l-fucopyranosyl-(1→4)]-2-acetamido-2-deoxy-β-d-glucopyranosyl-(1→3)-β-d-galactopyranoside, is presented to enable further investigation of the carbohydrate recognition process of H. pylori.     

天然产物(±)-Aiphanol的全合成研究

以醛1和5为起始原料,经几步反应后用Ag₂O偶联,得到含苯并二氧六环骨架的化合物7,化合物7经过选择性保护酚羟基,再用NaIO₄/OsO₄(cat.)氧化断裂双键,得到关键中间体9,化合物9和10经过Wittig-Horner反应,并用苯硫酚和AIBN实现了顺式双键向反式的转化,脱去保护基后完成了具有新颖结构的天然产物(±)-Aiphanol(12)的合成.     

Formal total synthesis of (±)-magellanine

Formal total synthesis of magellanine is described. Key features in the synthesis were stereoselective Ireland-Claisen rearrangement and intramolecular Pauson-Khand reaction of exo-cyclic enynes.     

Total synthesis of (±)-camphorataimides and (±)-himanimides by NaBH4/Ni(OAc)2 or Zn/AcOH stereoselective reduction

Maleic anhydride 1 of Antrodia camphorate, which can be isolated from Chinese herbal medicine, is achieved in which the longest linear sequence is only five steps, in 40% overall yield from commercially available succinic anhydride. The crucial antrodimides 3 and 2 can be readily transformed by the chemoselective reduction with Zn/AcOH and NaBH₄/Ni(OAc)₂·4H₂O to afford the naturally occurring camphorataimides, 4 and 5, in high yields as well, respectively. This synthetic strategy can also be modified to give access to a variety of different maleic acid derivatives, himanimides 6-8.     

Synthesis of (±)-aporphine utilizing Pictet-Spengler and intramolecular phenol ortho-arylation reactions

A synthesis of the alkaloid (±)-aporphine is reported. The initial key step of the synthesis involves a Pictet-Spengler cyclization of N-tosyl tyramine with 2-bromophenylacetaldehyde in trifluoroacetic acid. This step was followed by the second strategic transformation a palladium-mediated intramolecular phenol ortho-arylation reaction utilizing tricyclohexylphosphine as co-catalysts in the presence of cesium carbonate. Finally, de-oxygenation of the phenol, removal of the tosyl group and methylation gave the desired alkaloid.     

Total synthesis of (±)-megistophylline I

(±)-Megistophylline I (1), carrying a dienone residue in the acridone framework, was synthesized using the Claisen rearrangement to introduce a prenyl group as a key step.     

Intramolecular ortho-arylation of phenols utilized in the synthesis of the aporphine alkaloids (±)-lirinidine and (±)-nuciferine

A palladium-mediated intramolecular phenol ortho-arylation reaction applied to the construction of aporphine alkaloids is reported. Most significantly, the efficiency of this transformation was enhanced by the utilization of trialkylphosphine (i.e. tricyclohexylphosphine) or trialkylphosphonium salts (i.e. di-tert-butylmethyl-phosphonium tetrafluoroborate) as co-catalysts in the presence of cesium carbonate. This methodology was employed in the syntheses of the aporphine alkaloids (±)-lirinidine and (±)-nuciferine.     

Improved total synthesis of (±)-trans-dihydronarciclasine, devised for large-scale preparation

New synthetic route to (±)-trans-dihydronarciclasine, more suitable for a large-scale preparation, has been devised with the early stage incorporation of ester functionality for direct assembly of the B-ring lactam.     

Synthesis of substituted pyrrolidines and piperidines from endocyclic enamine derivatives. Synthesis of (±)-laburnamine

Functionalization of the α- and β-positions of readily available endocyclic enamine derivatives provides a convenient method for the formation of substituted pyrrolidines and piperidines. α-Alkoxy-β-iodopyrrolidines are formed by the electrophilic addition of iodine to the endocyclic enamine double bond of an N-substituted 2-pyrroline, and nucleophillic attack by an alcohol on the intermediate iodonium ion. The resultant α-alkoxy-β-iodopyrrolidines can be used in radical cyclization reactions to give bicyclic hemiaminal compounds, which can be further elaborated using N-acyliminium chemistry to form α,β-cis-dialkylsubstituted pyrrolidines. A strategy for the incorporation of amino functionality at the β-position was also established by using iodoamination of the enamine double bond, followed by migration of the amine functionality through an aziridination/methanolysis protocol. An alternative method uses an azidomethoxylation protocol using ceric ammonium nitrate (CAN) in the presence of NaN₃ and methanol. Formation and trapping of the N-acyliminium ions derived from these substrates, afforded the 3-carbamate and 3-azido-2-substituted products with good diastereoselectivity, with the preferential formation of the trans and cis stereoisomers, respectively. Using the sequential iodoamination, aziridination in methanol and N-acyliminium transformation, trans-3-NHCO₂Me-2-allyl-pyrrolidine was prepared, which was used as the key precursor in a synthesis of the natural 1-amidopyrrolizidine alkaloid, (±)-laburnamine.