Synthetic studies on bafilomycin A1: stereoselective synthesis of the enantiopure C1-C11 fragment

The synthesis of the enantiopure C₁-C₁₁ fragment of bafilomycin A₁ has been achieved with a 4% overall yield over 18 steps from (R)-(+)-citronellol. Key steps involve Sharpless asymmetric epoxidation, Miyashita reaction of a γ,δ-epoxymethacrylate with trimethylaluminum in the presence of water, bis-OTMS selective Swern oxidations, Corey-Fuchs alkyne formation, Negishi's carbometalation, and stereoselective formation of the C₂-C₃ trisubstituted bond of the conjugated diene by a Wittig-type olefination of the α,β-unsaturated C₃-C₁₁ aldehyde with the ylide derived from the readily available phosphonium salt [Cl⁻, Ph₃P⁺CH(OMe)COOMe].     

A Baylis-Hillman approach to the synthesis of C1-C11 fragment of caribenolide I

Stereoselective synthesis of C₁-C₁₁ fragment of caribenolide I, a potent antitumour macrolide isolated from a marine dinoflagellate Amphidinium sp. is described. The key steps rely on asymmetric aldol reactions, to control the absolute configurations of C₂, C₃ and C₁₀ stereogenic centres.     

Synthesis of the C17-C25 subunit of lasonolide A utilizing a Tsuchihashi-Yamamoto type rearrangement

An efficient synthesis of the C₁₇-C₂₅ subunit resident in (−)-lasonolide A is reported herein. The key reaction features that were utilized include a Tsuchihashi-Yamamoto type rearrangement and Molander-Reformatsky SmI₂ mediated intramolecular aldol reaction sequence. Lastly, a diastereoselective target oriented β-C-glycoside formation sequence via an oxocarbenium reduction completed the stereochemistry required for the completion of the C₁₇-C₂₅ segment of (−)-lasonolide A.     

Towards the total synthesis of Calyculin C: preparation of the C13-C25 spirocyclic core

A stereoselective synthesis of the C₁₃-C₂₅ of Calyculin C is described. Key steps involve the coupling of a terminal acetylene with a thiol ester and subsequent spirocyclisation using a double intramolecular hetero-Michael addition.     

Synthesis of the C1-C12 fragment of the tedanolides. Selective hydroboration-protonation of allylic alcohol approach

The combination of highly stereoselective vinyllithium addition and hydroboration-protonation of the resulting allylic alcohol permits the preparation of the completely protected C₁-C₁₂ fragment 2 of the novel macrocyclic cytotoxic agent tedanolide 1.     

Separation of C1-C5 aliphatic carboxylic acids on a highly sulfonated styrene-divinylbenzene copolymer resin column with a C6 aliphatic carboxylic acid solution as the mobile phase

Simultaneous separation of C₁-C₅ aliphatic carboxylic acids (formic, acetic, propionic, iso-butyric, butyric, iso-valeric and valeric acids) on a highly sulfonated styrene-divinylbenzene copolymer resin column (TSKgel SCX,  mm i.d.) was performed with C₆ aliphatic carboxylic acids (3-methyl-n-valeric, iso-caproic and caproic acids) solutions as the mobile phases. Using 0.05 mM sulfuric acid at pH 4.0 as the mobile phase, although good separation of these C₁-C₅ acids was achieved, peaks of the C₅ acids (iso-valeric and valeric acids) with large hydrophobicity tailed strongly. In contrast, using 1 mM C₆ acids at pH ca. 4.0 as the mobile phases, although vacant peaks corresponding to the C₆ acids in the mobile phase appeared, the peak shapes of the C₅ acids were improved greatly. Excellent simultaneous separation, symmetrical peaks and relatively high-sensitivity conductimetric detection for these C₁-C₅ acids were achieved on the TSKgel SCX column in 15 min with 1 mM iso-caproic acid at pH 4.0 as the mobile phase.     

An efficient synthesis of the C1-C14 subunit of (−)-lasonolide A via a target oriented β-C-glycoside formation sequence

An efficient synthesis of the C₁-C₁₄ subunit resident in (−)-lasonolide A is reported herein. The key reaction features that were utilized include a Molander-Reformatsky SmI₂ mediated intramolecular aldol reaction followed by a diastereoselective target oriented β-C-glycoside formation sequence. Lastly, a chemo- and diastereoselective cross-metathesis of a terminal olefin in the presence of a trisubstituted alkene with acrolein and subsequent olefination of the aldehyde moiety allowed for the completion of the (E,E)-diene side chain.     

A short approach to the bicyclo[4.3.0]nonane fragment of stawamycin

The bicyclo[4.3.0]nonane (C₁₁-C₂₁) fragment of stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(−)-3-hydroxy-2-methylpropionate. Key steps are a Pd-catalysed Stille coupling reaction between a vinyl iodide and a vinyl stannane followed by an intramolecular Diels-Alder cycloaddition reaction to give the desired adduct as the major isomer in 21% overall yield.     

Synthesis of the C5-C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction

The marine natural product cyclodidemniserinol trisulfate displayed moderate HIV-1 integrase inhibitory activity. Its novel structure triggered our interest to synthesize it. In our total synthesis effort, the natural product was dissected into four fragments based on the rational retrosynthetic analysis. All four fragments were successfully prepared with orthogonal protection. And the assembly of fragment A and B furnished the C₅-C₃₀ key subunit by employing the I₂-mediated deprotection and intramolecular ketal formation tandem reaction in the presence of NaHCO₃ in MeCN. Our work provided flexible and practical approaches to synthesize and derive the 3,5,7-trisubstituted 6,8-dioxabicyclo [3.2.1] octane based analogs to search for new structure HIV-1 integrase inhibitors.     

Stereoselective synthesis of the C14-C26 fragment of the cytotoxic macrolide FD-891

A stereoselective synthesis of the C₁₄-C₂₆ fragment of the naturally occurring, cytotoxic macrolide FD-891, is described. Asymmetric Evans aldol reactions and aldehyde Brown allylations are key steps of the synthesis.     

Qualitative and quantitative analysis of the n-alkanes C9-C17 and pristane in clean air masses

Summary An analytical method was developed for measuring n-alkanes (C₉ to C₁₇) and other hydrocarbons in tropospheric air with mixing ratios of a few ppt (10^–12) and higher. The hydrocarbons are collected in situ in absorption tubes, carefully protected against contamination and analysed later in the laboratory by gas chromatography. First data are reported for Atlantic air masses at the west coast of Ireland.

---

Qualitative und quantitative Analyse der n-Alkane C₉-C₁₇ und von Pristan in reiner Luft

Zusammenfassung Es wurde eine analytische Methode entwickelt zur Messung der n-Alkane (C₉ bis C₁₇) und anderer Kohlenwasserstoffe in reiner troposphärischer Luft mit Mischungsverhältnissen von einigen ppt (10^–12) und aufwärts. Die Kohlenwasserstoffe wurden am Beobachtungsort angereichert, sorgfältig gegen Verunreinigung geschützt und später im Laboratorium gas-chromatographisch analysiert. Erste Daten für atlantische Luftmassen an der Westküste Irlands werden mitgeteilt.

     

Stereoselective synthesis of a fully protected C13-C23 fragment of tedanolide

The combination of a high-yielding dienyllithium addition and a highly diastereoselective 1,2-reduction allows the preparation of the completely protected C₁₃-C₂₃ fragment 3 of the potent cytotoxic agent tedanolide 1. A convergent approach was used, namely a late stage coupling of the dienyllithium 16 with the selectively protected aldehyde 5 followed by oxidation-reduction and final epoxidation to give 3. The dienylstannane 4 was prepared from the dibromide 6 in five steps, the key step being the highly regio- and stereoselective stannylcupration of the alkyne 7. The commercially available hydroxy ester 10 was converted in 11 steps to the aldehyde 5. The compound 3 could potentially be a key intermediate for the synthesis of tedanolide 1.     

Stereoselective synthesis of the C1-C12 segment of iriomoteolide-1a: a very potent macrolide antitumor agent

A stereoselective synthesis of the C₁-C₁₂ segment of the potent cytotoxic macrolide, iriomoteolide 1a, has been accomplished. The key steps involve an enzymatic kinetic resolution of a β-hydroxy amide, a Pd-catalyzed cross-coupling to construct a substituted allylsilane, a highly and stereoselective conjugate addition of lithium dimethylcopper to an α,β-acetylenic ester and an elaboration of the C₆-C₇ trans-olefin geometry by a Julia-Kocienski olefination.     

Synthesis and molecular structures of heptafluoropropylated fullerenes: C70(n-C3F7)8, C70(n-C3F7)6O, and C70(C3F7)4

Ampoule reactions of C₇₀ with n- and i-C₃F₇I were carried out at 250-310 °C. Two step HPLC separations allowed the isolation of several C₇₀(n-C₃F₇)_4-8 and C₇₀(i-C₃F₇)₄ compounds. Crystal and molecular structures of C₇₀(n-C₃F₇)₈-V, C₇₀(n-C₃F₇)₆O, C₇₀(n-C₃F₇)₄, and three isomers of C₇₀(i-C₃F₇)₄ have been determined by X-ray crystallography using synchrotron radiation. Molecular structures of the new compounds were compared with the known examples and discussed in terms of addition patterns and relative energies of their formation.     

Diastereoselective synthesis of the 19-epi-C18-C25 segment of (−)-lasonolide A and an unusual inversion at C19

Diastereoselective construction of the 19-epi-C₁₈-C₂₅ segment of (−)-lasonolide A was achieved using a 5-exo-trigonal mode of radical cyclization for the creation of the contiguous quaternary and tertiary stereogenic centers at C₂₂ and C₂₃ as the key reaction step. During the dehydration stage, it was found that an unusual inversion of configuration took place.     

气相色谱-质谱表征甲醇制烯烃副产汽油中的C5～C7烯烃

采用气相色谱-质谱(GC-MS)对甲醇制烯烃(MTO)副产汽油中的C5~C7烯烃进行了详细的定性表征,对MTO副产汽油中的49个单烯烃、11个二烯烃和9个环烯烃共计69个C5~C7烯烃组分在聚甲基硅氧烷柱上的保留指数进行了测定和定性确认。根据GC-MS定性分析结果建立了MTO副产汽油中C5~C7烯烃的保留指数数据库,采用气相色谱对副产汽油中C5~C7烯烃组分进行了定量分析。定量结果表明:MTO汽油以C5~C7脂肪族烯烃为主,含有少量的二烯烃和环烯烃,烷烃和环烷烃含量很少。MTO副产汽油中C5~C7烯烃的详细表征为其综合利用提供了依据。     

High-temperature and photochemical syntheses of C60 and C70 fullerene derivatives with linear perfluoroalkyl chains

New experimental results on perfluoroalkylation of C₆₀ and C₇₀ with the use of R_fI (R_f = CF₃, C₂F₅, n-C₃F₇, n-C₄F₉, and n-C₆F₁₃), along with a critical overview of the existing synthetic methods, are presented. For the selected new fullerene (R_f)_n compounds we report spectroscopic, electrochemical and structural data, including improved crystallographic data for the isomers of C₇₀(C₂F₅)₁₀ and C₆₀(C₂F₅)₁₀, and the first X-ray structural data for the dodecasubstituted perfluoethylated C₇₀ fullerene, C₇₀(C₂F₅)₁₂, which possesses unprecedented addition pattern.     

A stereoselective synthesis of the C15-C25 subunit of (+)-lasonolide A

The C₁₅-C₂₅ upper THP segment 2 of (+)-lasonolide A has been synthesized efficiently via diastereomeric differentiation, iodocyclization and Julia-Kocieński's sulfone olefination to install its quaternary chiral center, cis-2,6-disubstituted THP and trans-olefin, respectively.     

离子色谱法测定合成气制烯烃产物中的C_1~C_6有机酸

采用离子色谱建立了合成气制烯烃(SGTO)水相产物和油相产物中C1~C6有机酸的测定方法。对分离条件进行了优化,使用标准样品测定了线性范围和工作曲线,考察了方法的精密度和准确度,确定了SGTO油相产物样品的碱洗条件,并对SGTO水相产物和油相产物样品进行了测定。结果表明:C1~C6有机酸的质量浓度在各自配制的质量浓度范围内呈现良好的线性关系,相关系数均大于0.99。标准溶液的回收率测定表明回收率在95.6%~104.3%之间,5次重复测定的相对标准偏差(RSD)在0.4%~3.6%之间,表明该方法具有良好的准确性和精密度。SGTO油相产物中的加标回收率在91.1%~96.8%之间,5次重复测定的RSD为0.7%~2.3%,准确性可以满足实际分析的需要。实际SGTO水相产物和油相产物中C1~C6有机酸的分析结果表明,SGTO水相产物中C2~C4有机酸含量较高,而SGTO油相产物中C4~C6有机酸含量较高。本研究对SGTO反应研究、催化剂制备、工艺优化以及设备材料的选择具有重要意义。