Synthesis and reactions of benzopentathiepin having hydroxyl group

The synthesis of benzopentathiepin having a hydroxyl group at the neighboring position of polysulfur ring was performed by demethylation of 6-ethyl-9-methoxybenzopentathiepin with hydrogenbromide. Benzotrithiole having hydroxyl group was not isolated at all. The hydroxyl group was also alkylated with alkyl iodide in the presence of weak base.     

A concise and practical synthesis of oseltamivir phosphate(Tamiflu) from d-mannose

A short and practical synthesis of oseltamivir phosphate was accomplished in 11 steps from inexpensive and abundant starting material, d-mannose. This synthetic route featured an intramolecular Horner–Wadsworth–Emmons reaction as the key step to furnish the cyclohexene ring product. The hydroxyl group was converted stereo specifically into an amino group by oxidation to the ketone and reductive amination whereas the second amino group was introduced by azide substitution of a hydroxyl group. This synthesis provided an economical and practical alternative for the synthesis of Tamiflu.     

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-beta-rotunol and all diastereomers of 6,11-spirovetivadiene

The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed by allylic oxidation at C8 and elimination of the tertiary hydroxyl group in the cyclohexane ring. On the other hand, elimination of the hydroxyl group in the side chain and reduction of the hydroxyl in the cyclohexane ring gave (-)-premnaspirodiene and (-)-hinesene. The synthesis of the rest of the diastereomers for these compounds required formal inversion of the C5 spiro carbon. The synthesis of these compounds showed that the structure of (-)-agarospirene isolated from Scapania sp. was erroneously assigned, and it has been corrected to be identical to that of (-)-hinesene.     

Synthesis of 4-alkoxy-8-hydroxyquinolines

Quinolines with a hydroxyl group at the 8-position and an alkoxy group at the 4-position are rare compounds. In this paper the synthesis of five 4-alkoxy-8-hydroxyquinolines is reported. The key reaction in the synthetic route is a selective protection of the hydroxyl group at C-atom 8 in 4,8-dihydroxyquinoline with a tosyl group and the hydrolytic removal of the protective group after the alkylation. The tosyl group is stable during the alkylations with various alkylating agents in the presence of sodium hydride.     

Advances in Protecting Groups for Oligosaccharide Synthesis

Carbohydrates contain numerous hydroxyl groups and sometimes amine functionalities which lead to a variety of complex structures. In order to discriminate each hydroxyl group for the synthesis of complex oligosaccharides, protecting group manipulations are essential. Although the primary role of a protecting group is to temporarily mask a particular hydroxyl/amino group, it plays a greater role in tuning the reactivity of coupling partners as well as regioselectivity and stereoselectivity of glycosylations. Several protecting groups offer anchimeric assistance in glycosylation. They also alter the solubility of substrates and thereby influence the reaction outcome. Since oligosaccharides comprise branched structures, the glycosyl donors and acceptors need to be protected with orthogonal protected groups that can be selectively removed one at a time without affecting other groups. This minireview is therefore intended to provide a discussion on new protecting groups for amino and hydroxyl groups, which have been introduced over last ten years in the field of carbohydrate synthesis. These protecting groups are also useful for synthesizing non‐carbohydrate target molecules as well.     

Palladium-catalyzed cross-coupling reactions of aryl mesylates

Palladium-catalyzed cross-coupling reactions are state-of-the art methods for synthesis of many important compounds. The development of the use of the phenol-derived sulfonated hydroxyl group in the coupling reactions is highly attractive as the hydroxyl group is commonly present in organic compounds and they are versatile alternatives to aryl halides in cross-coupling reactions. In this tutorial review, we summarize the current development of palladium-catalyzed cross-coupling reactions of aryl mesylates.     

有机硅试剂在药物合成中的应用

主要介绍了有机硅试剂作为保护剂对药物结构中含有羟基、羧基、不饱和键、氨基、羰基和其它官能团的保护及应用情况,以及在合成中间体烯醇硅醚等方面的应用.     

含羟基的青蒿倍半萜内酯差向异构体的合成

本文报道以青蒿酸(2)为原料合成了一些含羟基的青蒿倍半萜内酯差向异构体9与10、11与12、13与14。其中9已从青蒿中分离到。     

A simple one-pot entry to cyclic ethers of varied ring sizes from diols via phosphonium ion induced iodination and base catalyzed Williamson etherification

A novel and an efficient one-pot cyclization method using triphenylphosphine, iodine and a nitrogenous base has been established for the synthesis of cyclic ethers of various ring sizes. This appears to follow a two-step procedure, which includes preferential substitution of one hydroxyl group by an iodide generated in situ followed by an intramolecular ring closure through the attack of a free hydroxyl group or the more nucleophilic oxide ion.     

3-羟甲基氮杂环丁烷盐酸盐的实用合成方法

氮杂环丁烷类化合物是一类重要的饱和四元含氮杂环化合物,在药物研发中有着广泛的应用。本文以二苯甲胺和环氧氯丙烷为起始原料,在碱性条件下反应关环构建N-杂环丁烷母核,之后依次发生羟基的氧化、Wittig反应生成环外双键,随后采用硼氢化氧化反应将双键转化为羟甲基,最后氢化脱去二苯甲基得到目标产物3-羟甲基氮杂环丁烷,反应的5步转化总收率为40%。该合成方法操作简单,原料廉价易得,避免了剧毒试剂的使用,具有很好的工业化前景。     

Protecting-group-based colorimetric monitoring of fluorous-phase and solid-phase synthesis of oligoglucosamines

A new hydroxyl protecting group, nitrophthalimidobutyric (NPB) acid, has been synthesized in one solvent-free step for colorimetric monitoring of reaction cycles upon its facile removal with hydrazine acetate in the solid-phase and fluorous-phase syntheses of antigenic oligoglucosamines associated with infectious Staphylococcus aureus. The NPB group serves as a convenient hydroxyl protecting group that is stable to the basic conditions required for the synthesis of the common trichloroacetimidate protecting groups, the strongly acidic conditions used in glycosylation reactions, as well as conditions commonly used to remove silicon-based protecting groups.     

Regioselective inversion of the hydroxyl group in D-ribo-phytosphingosine via a cyclic sulfate and bis-sulfonate intermediate

The selective synthesis of D-xylo- and D-lyxo-phytosphingosines from commercially available D-ribo-phytosphingosine is described. Thermolysis of the N-carbonyl protected cyclic sulfate led to an inversion of configuration of the proximal hydroxyl group to give the xylo-isomer, whereas the corresponding bis-sulfonate resulted in an inversion of configuration of the distal hydroxyl group to give the lyxo-isomer. This study allowed the comparison between a cyclic sulfate and a bis-sulfonate in an intramolecular substitution reaction involving a carbonyl oxygen nucleophile.     

The N-hydroxymethyl group for stereoselective conjugate addition: application to the synthesis of (-)-statine

[reaction: see text] Efficient synthesis of enantiomerically pure (-)-statine was achieved with the stereoselective intramolecular conjugate addition of the hydroxyl group tethered to the amino group of a configurationally stable N-Boc-L-leucinal derivative.     

Synthesis of a pentasaccharide fragment of varianose, a cell wall polysaccharide from Penicillium varians

The first synthesis of an oligosaccharide fragment of varianose, a polysaccharide produced by Penicillium varians, is reported. The target pentasaccharide features both alpha- and beta-galactofuranoside residues and the alpha-galactofuranoside residue is hindered, being substituted on adjacent oxygens (O1 and O2), both of which are cis to the two-carbon side chain at C4. Key features of the synthesis include a novel method for the selective protection of the C3 hydroxyl group of galactofuranosyl residues via an epoxide formation/opening sequence, the introduction of the alpha-d-galactofuranosyl residue using a 2,3-anhydrosugar donor, and the use of the 1-benzenesulfinylpiperidine/trifluoromethanesulfonic anhydride activation method for the addition of an alpha-D-glucopyranosyl residue to a hindered hydroxyl group in an advanced tetrasaccharide intermediate.     

An enantioselective total synthesis of (+)-aigialospirol

A concise and enantioselective total synthesis of (+)-aigialospirol is described here, featuring the first complex natural product synthesis that employs a cyclic ketal-tethered ring-closing metathesis strategy and an unexpected stereoselective epimerization of a benzylic hydroxyl group. The 15-step synthetic sequence illustrates the proof-of-concept that such an approach can be competitive with the classical spiroketal formation in the natural product synthesis.     

Total synthesis of (+)-allocyathin B2

The first enantioselective synthesis of (+)-allocyathin was achieved. The synthesis features a Pd-catalyzed asymmetric allylic alkylation to install the first quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. The unusual olefin isomerization of the Ru-catalyzed cycloisomerization was discussed and exploited for the synthesis.     

Reactivity of Aliphatic and Phenolic Hydroxyl Groups in Kraft Lignin towards 4,4′ MDI

Several efforts have been dedicated to the development of lignin-based polyurethanes (PU) in recent years. The low and heterogeneous reactivity of lignin hydroxyl groups towards diisocyanates, arising from their highly complex chemical structure, limits the application of this biopolymer in PU synthesis. Besides the well-known differences in the reactivity of aliphatic and aromatic hydroxyl groups, experimental work in which the reactivity of both types of hydroxyl, especially the aromatic ones present in syringyl (S-unit), guaiacyl (G-unit), and p-hydroxyphenyl (H-unit) building units are considered and compared, is still lacking in the literature. In this work, the hydroxyl reactivity of two kraft lignin grades towards 4,4′-diphenylmethane diisocyanate (MDI) was investigated. ³¹P NMR allowed the monitoring of the reactivity of each hydroxyl group in the lignin structure. FTIR spectra revealed the evolution of peaks related to hydroxyl consumption and urethane formation. These results might support new PU developments, including the use of unmodified lignin and the synthesis of MDI-functionalized biopolymers or prepolymers.     

Total synthesis of the heptasaccharide repeating unit of the iron-binding exopolysaccharide secreted by Klebsiella oxytoca BAS-10

The first total synthesis of a heptasaccharide found in the iron-binding exopolysaccharide produced by Klebsiella oxytoca BAS-10 has been achieved in excellent yield using a block synthetic strategy. A trisaccharide glycosyl donor was stereoselectively coupled with a tetrasaccharide glycosyl acceptor using the trichloroacetimidate activation procedure. The yields and stereo outcome were excellent in each step of glycosylation. A late stage oxidation protocol was adopted for the oxidation of the primary hydroxyl group to the carboxylic functionality while keeping a secondary hydroxyl group unaffected.     

First stereoselective total synthesis and reconfirmation of absolute structure of nonenolide (−)-stagonolide D

The first stereoselective total synthesis of nonenolide (?)-stagonolide D has been accomplished. Midland Alpine borane reduction to install hydroxyl group at C4, Henbest epoxidation to introduce epoxide stereoselectively between C7 and C8, Yamaguchi esterification and Olefin metathesis reaction are the key steps involved in the total synthesis.     

Total synthesis of gymnocin-A

A highly convergent total synthesis of gymnocin-A, a cyctotoxic polyether marine natural product, has been achieved. The synthesis features Suzuki-Miyaura coupling of the ABCD and FGHIJKLMN rings, stereoselective introduction of the C17 hydroxyl group, ring-closure of the F ring, and a late-stage incorporation of a 2-methyl-2-butenal side chain.