Studies towards the total synthesis of Sch 56036; isoquinolinone synthesis and the synthesis of phenanthrenes

The isoquinolinone hemisphere of Sch 56036 has been prepared using a modified Pomeranz-Fritsch reaction and the synthesis of the phenanthrene core has been modelled via a Suzuki coupling and subsequent ring closing metathesis.     

Total synthesis of apoptolidin: completion of the synthesis and analogue synthesis and evaluation

The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner-Wadsworth-Emmons coupling of fragments 22 and 25. The final stages of the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane 2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection. The developed synthetic technology was applied to the construction of several analogues including 74, 75, and 77 which exhibit significant bioactivity against tumor cells.     

Benzothiazines in synthesis. Toward the synthesis of pseudopteroxazole

[reaction: see text] The tricyclic benzothiazine 15 was prepared in a straightforward fashion via a completely stereoselective intramolecular Friedel-Crafts alkylation. This compound represents a potential precursor to the antitubercular agent, pseudopteroxazole. Its synthesis proceeded via a completely selective, intramolecular addition of a sulfoximine-stabilized carbanion to an alpha,beta-unsaturated ester, followed by functional group manipulations.     

Studies toward the total synthesis of vinigrol. synthesis of the octalin ring

[reaction: see text] Herein, we disclose our results regarding various strategies toward the assembly of the octanyl ring of vinigrol. Attempts to generate the problematic eight-membered ring through a ring expansion or via unification of the terminal olefins using the ring-closing metathesis were not successful. The cyclooctane ring was created via a sequential hydroxy Diels-Alder/Claisen rearrangement reaction of diene 55 and N-benzylmaleimide.     

Toward the synthesis of thapsigargin: enantioselective synthesis of 7,11-dihydroxyguaianolides

[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.     

Total synthesis of everninomicin 13,384-1--Part 3: synthesis of the DE fragment and completion of the total synthesis

The stereoselective construction of the DE fragment (2) of everninomicin 13,384-1 (1) is reported. From the two possible ways of inserting the DE fragment between the A1B(A)C and FGHA2 domains of the natural product, the sequence involving the DEFGHA2 segment was found to be the most viable. This coupling was followed by attachment of a suitably protected and activated A1B(A)C fragment which led, after orthoester construction and final deprotection to the targeted everninomicin 13,384-1 (1), completing the total synthesis of this complex naturally occurring substance.     

离子热法合成沸石咪唑骨架材料及其溶解-结晶机理研究

基于沸石咪唑骨架材料在离子液体和低共熔溶剂中冷却结晶的析出方式,开发了一种离子热法合成沸石咪唑骨架材料的新途径,采用X射线衍射、扫描电镜、核磁共振光谱、红外光谱以及热重分析等方法对制备的产物进行了表征,研究了合成条件对产物结晶度、尺寸和形貌的影响,探讨了沸石咪唑骨架材料在离子热合成体系中的溶解-结晶析出机理.研究发现,冷却速率能够影响产物形貌,急速冷却时,sod(RCSR代码)型产物的形貌为球形,zni(RCSR代码)型产物为棒状或平板状;程序控制冷却时,sod型产物的形貌为多面体,zni型产物呈团簇状.     

Studies on the total synthesis of lactonamycin: synthesis of the CDEF ring system

A concise and efficient synthesis of the tetracyclic CDEF ring system of lactonamycin (1) is described. The key step involved the Lewis acid mediated, intramolecular Friedel-Crafts acylation of carboxylic acid 6 to produce the tetracyclic CDEF core structure of target 1. The synthesis of 6 was carried out using a high-yielding Negishi coupling of benzyl bromide 7 with triflate 8, which was accessible in 11 steps and 31% overall yield on a multigram scale starting from trihydroxy acid 9.     

Progress toward the total synthesis of (+)-aldosterone: synthesis of the A-D rings

[reaction: see text] Synthesis of the A-D rings of the cortical hormone (+)-aldosterone is described. The key step incorporates a chiral tether in a type 2 intramolecular Diels-Alder reaction that establishes the absolute configuration of four contiguous asymmetric centers. This approach provides an efficient route for either enantiomer of the steroid skeleton.     

Applications of the sulfinimine-mediated asymmetric strecker synthesis to the synthesis of alpha-alkyl alpha-amino acids

Addition of Et(2)AlCN and i-PrOH to ketosulfinimines (N-sulfinyl imines) affords corresponding alpha-alkyl alpha-amino nitriles in moderate to good yields. The diastereoselectivity is largely dependent on the E/Z isomer ratio of the ketosulfinimine. Hydrolysis of the diastereomerically pure amino nitriles affords enantiopure alpha-alkyl alpha-amino acids in moderate to good yields.     

Toward the total synthesis of FR901483: concise synthesis of the azatricyclic skeleton

A concise synthesis of the azatricyclic core of FR901483 has been accomplished using a novel strategy that involves a nucleophilic addition to an N-acyl iminium ion, a ring-closing metathesis, a diastereoselective hydroboration, and a lactone-lactam rearrangement that worked well in a preliminary model study. Extension of this approach to the synthesis of a more highly functionalized intermediate that could be transformed into (-)-FR901483 first required the development of a new protecting group, the 1-ethylallyloxycarbamate group, for amines that may be removed under mild conditions. However, because the stereoselectivity in a key step in which a functionalized allyl zinc reagent was added to an intermediate hydroxy-substituted imine was low, this route to (-)-FR901483 is no longer being pursued.     

New synthesis of vaulted biaryl ligands via the Snieckus phenol synthesis

[reaction: see text] In an effort to develop a synthesis of the VAPOL ligand that avoids the use of a chromium carbene complex, a route was examined that involved the annulation of a naphthalene carboxamide via the method of Snieckus. The latter derivatives could be converted in a two-step sequence to 2-phenyl-4-phenanthrols in 60-72% overall yields. The utility of this method for the synthesis of VAPOL derivatives is demonstrated in the synthesis of (S)-7,7'-dimethyl-VAPOL.     

Benzothiazines in synthesis: studies directed toward the synthesis of erogorgiaene

The use of benzothiazenes for the formal total synthesis of erogorgiaene and stereoselective total syntheses of two diastereomers of this natural product is described. In particular, the stereochemical course of a radical cyclization anticipated to give the correct relative stereochemistry for the synthesis of erogorgiaene is discussed utilizing both experimental and computational data.     

Total synthesis of the eupomatilones

Full details of the total syntheses of five members of the eupomatilone family of lignans are reported.     

Studies toward the total synthesis of azaspiracids: synthesis of the FGHI ring domain

Synthesis of the FGHI ring domain of azaspiracids, the causative agents for a new type of shellfish poisoning, azaspiracid poisoning (AZP), has been achieved. The synthesis features dithiane anion-epoxide coupling for convergent fragment assembly.     

Direct synthesis of the beta-l-rhamnopyranosides

The direct formation of beta-l-rhamnopyranosides by means of thioglycoside donors protected with a 2-O-sulfonate ester and, ideally, a 4-O-benzoyl ester, is reported. Activation is achieved with the combination of 1-benzenesulfinyl piperidine and triflic anhydride in the presence of 2,4,6-tri-tert-butylpyrimidine. Selectivities vary from moderate to good, and the sulfonyl group is easily removed post-glycosylation with sodium amalgam in 2-propanol.     

Total synthesis of the mycolactones

[structure: see text] The first total synthesis of the mycolactones is reported. This work unambiguously confirms our earlier relative and absolute stereochemical assignment of the mycolactones.     

Mechanism of the heterodiene synthesis

The kinetics of the reaction of diethyl azodicarbonate with various oxazoles were studied, and a model of the activated complex with partial separation of the charges of opposite sign is proposed. The results of the calculations, which were made via the Hückel MO method, are in good agreement with the two-step mechanism of the heterodiene synthesis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 600–607, May, 1973.The authors thank A. S. Ol'khovyi and V. G. Tumanyan for their assistance in performing the calculations.     

Kinetics of the carnallite synthesis

The kinetics of the carnallite synthesis from crystalline KCl and a MgCl₂ solution at temperatures from 20 up to 100°C was studied. The temperature dependence of the conversion degree was determined. The activation energy and the rate constant of the carnallite synthesis in the temperature range of 30–60°C were determined.