The first transannular [4+3] cycloaddition reaction: synthesis of the ABCD ring structure of cortistatins

A 14-membered macrocycle with an allene and a furan strategically located at across the ring from each other is synthesized using an allene ring closing metathesis reaction. Upon treatment of the macrocycle with a catalytic amount of Pd(OAc)₂ and other additives, the first transannular [4+3] cycloaddition occurred to yield 37% of a tetracyclic compound containing the ABCD ring structure of the natural products cortistatins.     

Total synthesis of the ristocetin aglycon

The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively diastereoselective (3:1, 86%) Suzuki coupling for installation of the AB biaryl linkage on which the atropisomer stereochemistry can be further thermally adjusted, and an effective macrolactamization (51%) for closure of the 12-membered AB ring system. A similarly effective 13-step (14% overall) synthesis of the 14-membered EFG ring system 4 was implemented employing a room-temperature intermolecular S(N)Ar reaction of an o-fluoronitroaromatic for formation of the FG diaryl ether (69%) and a key macrolactamization (92%) with formation of the amide linking residues 1 and 2. The two key fragments 3 and 4 were coupled, and the remaining 16-membered DE ring system was closed via diaryl ether formation to provide the ristocetin tetracyclic ring system (15 steps, 8% overall) enlisting an unusually facile (25 degrees C, 8 h, DMF, >/=95%) and diastereoselective (>/=15:1) aromatic nucleophilic substitution reaction that benefits from substrate preorganization.     

Gold-catalyzed transannular [4+3] cycloaddition reactions

In the presence of a catalytic amount of Au(I) and Ag(I) salts, the 14-membered furanophane II with an allene function located across the ring undergoes both a transannular [4+3] and [4+2] cycloaddition. Secondary rearrangement products containing a tricyclic ring system were isolated when the catalyst was PtCl₂.     

数据挖掘辅助定向合成(Ⅰ)具有特定孔道结构的微孔磷酸铝

采用决策树方法对微孔磷酸铝的合成反应数据库进行了数据挖掘研究, 结果表明, 有机胺模板剂的属性对特定孔道的生成起着至关重要的作用. 进一步分析得到合成十二元环AlPO4-5微孔磷酸铝的约束条件, 并从理论上预测出用于合成十二元环AlPO4-5微孔磷酸铝的一系列新的有机胺模板剂. 部分理论分析结果得到了分子力学计算的有力支持, 并被合成实验所验证.     

Synthesis of α-hydroxyalkyl dehydroazepanes via catalytic enantioselective borylative migration of an enol nonaflate

A Pd-catalyzed borylative migration methodology for cyclic enol perfluorosulfonates was applied to the synthesis of the corresponding 7-membered, azepane ring system. Throughout the optimization, it was shown that the reaction is sensitive to the nitrogen protecting group as well as the type of base and solvent. The resulting cyclic allylboronate reacts stereoselectively with aldehydes for the synthesis of novel α-hydroxyalkyl dehydroazepanes in good yield and enantioselectivity over two steps. We highlight the utility of this methodology with an efficient synthesis of the de novo 7-membered ring analogue of the piperidine alkaloid β-conhydrine.     

A three-carbon (n+1+2) ring expansion method for the synthesis of macrocyclic enones. Application to muscone synthesis

The three-carbon ring expansion methodology commences with the preparation of a cyclic allene (C9, C11, C13), readily available from the corresponding cycloalkene via dibromocarbene addition and subsequent treatment with methyllithium. Dichloroketene addition to the cyclic allene regioselectively provides the [2+2] cycloadduct, which is reductively dechlorinated with zinc in methanol. The resulting cyclobutanone is then catalytically hydrogenated; cyclobutanone ring opening is affected with trimethylsilyl iodide; immediate dehydroiodination of the resulting β-iodocycloalkanone with diazabicycloundecane (DBU) provides the corresponding macrocyclic enone. The 15-membered enone was converted to d,l-muscone with (CH₃)₂CuLi.     

Rhodium-catalysed tetradehydro-Diels–Alder reactions of enediynes via a rhodium-stabilized cyclic allene

Efficient methods for the synthesis of fused-aromatic rings is a critical endeavour in the creation of new pharmaceuticals and materials. A direct method for preparing these systems is the tetradehydro-Diels–Alder reaction, however this is limited by the need for harsh reaction conditions. A potential, but underdeveloped, route to these systems is via transition metal-catalysed cycloaromatisation of ene-diynes. Herein, tethered unconjugated enediynes have been shown to undergo a facile room-temperature Rh^I-catalysed intramolecular tetradehydro-Diels–Alder reaction to produce highly substituted isobenzofurans, isoindolines and an indane. Furthermore, experimental and computational studies suggest a novel mechanism involving an unprecedented and complex Rh^I/Rh^III/Rh^I/Rh^III redox cycle involving the formation of an unusual strained 7-membered rhodacyclic allene intermediate and a Rh^III-stabilized 6-membered ring allene complex.

Room temperature Rh-catalysed tetradehydro-Diels–Alder reaction via an unusual Rh-stabilised allene.     

The synthesis,characterization, and structure solution of SSZ-58: a novel two-dimensional 10-ring pore zeolite with previously unseen double 5-ring subunits

The synthesis, structure solution, and characterization of the novel zeolite SSZ-58 are described. SSZ-58 was synthesized under hydrothermal conditions using 1-butyl-1-cyclooctylpyrrolidinium cation as a structure-directing agent. The framework topology of SSZ-58 was determined with the FOCUS Fourier recycling method. SSZ-58 possesses 12 tetrahedral atoms in the asymmetric unit of its highest topological symmetry, and to date it is the most complex zeolite structure solved from powder data. Rietveld refinement of synchrotron powder X-ray diffraction data in space group Pmma confirmed the proposed model. SSZ-58 contains layers of atoms that are linked together by double five-membered rings (D5R), or 5(2)4(5) subunits, that have not been observed before in any zeolite or zeotype structures. SSZ-58 possesses a two-dimensional channel system consisting of 10-membered ring pores that intersect to form large cavities circumscribed by 12- and 16-membered ring pores.     

Synthesis and stereochemical elucidation of a 14-membered ring phosphonate

[structure: see text]. We report the synthesis and stereochemical elucidation of a 14-membered ring phosphonate. The key step in the synthesis of the macrolide phosphonate was the cyclization of the acyclic precursor using the Mitsunobu reaction, a mild reaction for the preparation of mixed phosphonates.     

Total synthesis of pyridomycin

The first total synthesis of pyridomycin is described including the stereocontrolled construction of the exocyclic (Z)-s-butylidene moiety in the 12-membered ring system.     

Synthesis and characterisation of medium-sized ring systems by oxidative cleavage. Part 2: Insights from the study of ring expanded analogues

Variable temperature NMR analysis and computational methods have been used to develop a detailed understanding of the ¹H NMR spectra of a family of medium-sized ring containing compounds. The family consists of analogues containing 10-, 11- and 12-membered rings and in all cases the NMR spectra at room temperature showed a series of diastereotopic methylene signals despite the lack of a stereogenic centre in these systems. On repeating the NMR analysis at higher temperatures, all the signals coalesced for the 12-membered ring system consistent with full interconversion of ring conformers. This was not observed in the analogous 10- and 11-membered ring systems with the interchange of conformers remaining slow on the NMR timescale. However, 1D gs-NOESY/EXSY NMR experiments showed that in the smaller ring systems interconversion of diastereotopic protons did occur. Computational studies suggest that the dynamic process observed by NMR for the 10- and 11-membered rings systems is different from that observed in the 12-membered ring containing compound.     

Synthesis of the (S,S,S)-diastereomer of the 15-membered biaryl ring system of RP 66453

The synthesis of the 15-membered biaryl ring system constituting an appropriately functionalized AB ring system of RP 66453 is detailed.     

Alcaloides du Peripterygia marginata (baill.) loes. (célastracées)—II : Synthèses totales dans la série de la (±) périphylline

Unequivocal total synthesis of an 8-membered ring isomer A and a 13-membered ring isomer B assisted the structural determination of periphylline, an alkaloid derived from spermidine.     

Construction of a pentacyclic ring system of isoryanodane diterpenoids by SmI2-mediated transannular cyclization

Isoryanodane diterpenoids possess a densely oxygenated and intricately fused pentacycle (ABCDE-ring), although its unique ring system has not yet been assembled chemically. The 6/5/7-membered BCD-rings of isoryanodanes differ from the 5/6/6-membered rings of the structurally-related ryanodanes. We previously achieved the total synthesis of ryanodine and five other ryanodane diterpenoids by employing the common ABDE-tetracyclic intermediate 1. Herein, we report a new strategy for constructing isoryanodane ABCDE-ring structure 3 from 1 via a combination of the oxy-Cope rearrangement and SmI₂-mediated transannular cyclization.     

Synthetic studies on stevastelins. 1. Total synthesis of stevastelins B and B3

[Chemical reaction: See text] The synthesis of stevastelin B3 (2) and B (5) are described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a promising candidate for the synthesis of the [15]-membered ring members of the stevastelins; however, the oxirane ring opening, required for the completion of the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B (5), carrying out the oxirane ring opening earlier in the synthesis and following a synthetic scheme capable of delivering analogues. On the other hand, a translactonization reaction of the [15]-membered ring derivative 59 led to the total synthesis of the natural [13]-membered ring component of the stevastelins family, stevastelin B3 (2).     

Umamidierungsreaktionen an cyclischen Amino-amid-Systemen. 3. Mitteilung über Umamidierungsreaktionen

Transamidation Reactions with Cyclic Amino-amides Lactames which are substituted at the nitrogen atom by a 3-aminopropyl residue are transformed under base catalysis to cyclic amino-amides enlarged by 4 ring atoms. The formed ring must be at minimum 12-membered. Scheme 2 illustrates this result: the 8-membered 7 is transamidated in 96% yield to the 12-membered ring 8 (in the presence of potassium 3-aminopropylamid in 1, 3-propanediamine), the 9-membered 10 to the 13-membered ring 11 (97%) and the 11-membered 14 to the 15-membered ring 15 . Furthermore, the 13-membered ring 27 (Scheme 5) is transformed to the 17-membered 28 . In the case of the 15-membered lactame 15 it is demonstrated that 14 is not formed back under the conditions of the transamidation. Large ring lactames which are substituted at the nitrogen atom by a 3-(alkylamino) propyl group lead under base catalysis to an equilibrium mixture, e.g. the 17-membered 26 is in equilibrium with the 21-membered 29 . This result is similar to the behavior of the corresponding open-chain amino-amides [2]. Because of transannular interactions, the 11-membered ring 2 is not stable: transamidation of the 7-membered 1 (Scheme 1) doesn't give the expected 2 , but its water elimination product 3 in small yield. The N-tosyl derivative of 2 , namely 20 , is synthesized by an independent route (Scheme 3). Detosylation of 20 yields the 7-membered 1 instead of 2 . Concerning the mechanism of this interesting reaction see Scheme 4.     

A Photochemical Approach to the Bicyclo [5.3.1] Undecane Ring System of Taxane Diterpenes

The bicyclo [5.3.1] undecane derivative 12, an important structural element of the taxane diterpenes, was prepared by photocycloaddition of the bicyclo [3.3.1] dione 9 to allene followed by cyclobutane ring opening (the de Mayo reaction).     

First and second generation total synthesis of the teicoplanin aglycon.

Full details of studies leading to the total synthesis of the teicoplanin aglycon are provided. Key elements of the first generation approach (26 steps from constituent amino acids, 1% overall) include the coupling of an EFG tripeptide precursor to the common vancomycin/teicoplanin ABCD ring system and sequential DE macrocyclization of the 16-membered ring with formation of the diaryl ether via a phenoxide nucleophilic aromatic substitution of an o-fluoronitroaromatic (80%, 3:1 atropisomer diastereoselection) followed by 14-membered FG ring closure by macrolactamization (66%). Subsequent studies have provided a second generation total synthesis which is shorter, more convergent, and highly diastereoselective (22 steps, 2% overall). This was accomplished by altering the order of ring closures such that FG macrolactamization (95%) preceded coupling of the EFG tripeptide to the ABCD ring system and subsequent DE ring closure. Notably, DE macrocyclization via diaryl ether formation on substrate 57, the key intermediate in the latter approach incorporating the intact FG ring system, occurred with exceptional diastereoselection for formation of the natural atropisomer (>10:1, 76%) without problematic C(2)(3) epimerization provided the basicity of the reaction is minimized.     

A taxane with a novel 9α,13α-oxygen bridge from Taxus cuspidata needles

A novel taxane with an unprecedented hemiacetal ring between C-13 and C-9 was isolated from the needles of Taxus cuspidata. The structure was characterized as (12αH)-2α,10β-diacetoxy-5α-cinnamoyloxy-9α,13α-epoxytax-4(20)-ene-11β,13β-diol (1). This is the first example of a natural taxane with a C-13 and C-9 oxygen bridge to form an unusual 6/8/6/6-membered ring system.     

Stereocontrolled total synthesis and biological evaluation of (−)- and (+)-petrosin and its derivatives

Total synthesis of (−)- and (+)-petrosin was accomplished. Stereocontrolled construction of the quinolizidine ring was achieved through a diastereoselective Mannich reaction and an aza-Michael reaction. Head-to-tail dimerization was performed by assembly of the two monomers using Suzuki–Miyaura cross coupling and subsequent ring-closing metathesis to construct the 16-membered ring. Biological evaluation of synthetic (−)- and (+)-petrosin and its derivatives indicated that the bispiperidine structure was necessary for the inhibition of syncytium formation.