Total Synthesis of Crotophorbolone

The complex ABC‐tricyclic structure of crotophorbolone, a derivative of the tigliane diterpenoids, was assembled by coupling of simple fragments. The six‐membered C‐ring fragment, having five contiguous stereocenters, was stereoselectively constructed from (R)‐carvone. After attachment of the five‐membered A‐ring through the π‐allyl Stille coupling reaction, the α‐alkoxy bridgehead radical reaction effected the endo‐cyclization of the seven‐membered B‐ring by forming the sterically congested bond at C9 and C10 stereospecifically and stereoselectively, respectively. Finally, the functional groups on the 5/7/6‐membered ring system were manipulated by rhodium‐catalyzed C2 olefin isomerization, C13 decarboxylative oxidation, and C4 hydroxylation, thus completing the first total synthesis of crotophorbolone.     

Correlation of ring nitrogen substituents with carbon-13 nuclear magnetic resonance data in azoloazines

Carbon–13 nuclear magnetic resonance data have been acquired on 22 azoloazines. Chemical shifts have been correlated by a step–wise linear multiple regression with nitrogen substituents in both the 5- and 6-membered rings using pyrrolo[1,2-α]pyridine as the reference for chemical shift correlation. The data demonstrate that a highly correlated set of chemical shift parameters exist. Nitrogen substitution in the five–membered ring produces larger cross–ring effects than are oberved in the five–membered ring when substitution occurs in the six–membered ring. Within the six–membered ring a constant para- substituent parameter is noted. The meta- and para- parameters are more complex and fall into two groups for each parameter. Within the five–membered ring, a highly regular chemical shift pattern is observed which reflects an attenuated perturbation from nitrogen substitution in the six–membered ring.     

Visible‐Light‐Driven Strain‐Increase Ring Contraction Allows the Synthesis of Cyclobutyl Boronic Esters

There are a limited number of ring‐contraction methodologies which convert readily available five‐membered rings into strained four‐membered rings. Here we report a photo‐induced radical‐mediated ring contraction of five‐membered‐ring alkenyl boronate complexes into cyclobutanes. The process involves the addition of an electrophilic radical to the electron‐rich alkenyl boronate complex, leading to an α‐boryl radical. Upon one‐electron oxidation, ring‐contractive 1,2‐metalate rearrangement occurs to give a cyclobutyl boronic ester. A range of radical precursors and vinyl boronates can be employed, and chiral cyclobutanes can be accessed with high levels of stereocontrol. The process was extended to the preparation of benzofused cyclobutenes and the versatility of the boronic ester was demonstrated by conversion to other functional groups.     

Two New Bis-tetrahydrofuran Ring Annonaceous Acetogenins from the Roots of Uvaria calamistrata

Althoughourresearchrevealedthatnarumicin-IIanddesacetyluvaricinwerethetwomajorbioactivebis-THFringacetogeninsintherootsofUvariacalamistralaHance,twonewbis-THFringannonaceousacetogeninswithmild-activitiesnamedcalamistrinsF(l)andG(2)hadalsobeenisolated.TheacetogeninsweretraceconstituentsintheplantandstructurallyhadthecharacteristicsofOH-flankedTHFringfromC-l8toC-25andathirdOHgroupatC-5.lwasisolatedaswaxysolid.TheFABMSoflgave[MH1 peakatm/:623,which,combiningwithelementalanaIysis,sugge…     

Ringerweiterungsreaktionen von N-(2-Aminoäthyl)-, N-(4-Aminobutyl)-, N-(6-Amino-4-aza-hexyl)- und N-(8-Amino-4-aza-octyl)-lactamen. 7. Mitteilung über Umamidierungsreaktionen

Ring Enlargement Reactions of N -(2-Aminoethyl)- , N -(4-Aminobutyl)- , N -(6-Amino-4-aza-hexyl)- and N -(8-Amino-4-aza-octyl)-lactames The N-aminoalkyl-lactams 1 , 3 , 4 , 10 (Scheme 2) and 13 (Scheme 3) have been synthesized. In the presence of KAPA (potassium 3-aminopropylamide in 1,3-propanediamine) 1 is stable, whereas 3 , 4 and 10 rearrange under ring enlargement to 5 , 8 and 11 , respectively. The 4-aminobutyl derivate 13 rearranges in a fast reaction to 14 ; after a longer reaction time the 22membered ring 16 and the ring opened product 18 are formed. Hence it may be concluded that the 7membered lactam ring is more stable than the 10membered one, and the 11membered lactam ring is more stable than the 8 membered one. Moreover, the 5- and 6 membered ring intermediates of these transamidation reactions are prefered to the 7membered ring intermediates (cf. [10]).     

五元氮杂环的开环反应研究进展

综述了近年来各种五元氮杂环的开环反应及其在有机合成中的应用。杂环化合物在有机合成中的作用越来越重要,五元氮杂环是其中最重要的一部分,其开环反应可以用来合成某些用其它方法难以合成的多官能团化合物,或通过开环和修饰合成其它环状化合物,还可以作为保护基以及研究仿生合成领域中各类复杂的生化反应等。     

Vinylogous dieckmann condensation: an application of Baldwin's rules.

Vinylogous Dieckmann condensations equivalent to enolexo-exo-trig and enolendo-exo-trig cyclisations have been investigated. Five membered rings were smoothly obtained from the former whereas the latter cyclisations occurred with six but not with five membered ring systems.     

Medium‐Sized‐Ring Analogues of Dibenzodiazepines by a Conformationally Induced Smiles Ring Expansion

Analogues of dibenzodiazepines, in which the seven‐membered nitrogen heterocycle is replaced by a 9–12‐membered ring, were made by an unactivated Smiles rearrangement of five‐ to eight‐membered heterocyclic anthranilamides. The conformational preference of the tertiary amide in the starting material leads to intramolecular migration of a range of aryl rings, even those lacking electron‐withdrawing activating groups, and provides a method for n →n +4 ring expansion. The medium‐ring products adopt a chiral ground state with an intramolecular, transannular hydrogen bond. The rate of interconversion of their enantiomeric conformers depends on solvent polarity. Ring size and adjacent steric hindrance modulate this hidden hydrophilicity, thus making this scaffold a good candidate for drug development.     

Diverse guaiane-type sesquiterpenoids from the root of Daphne genkwa based on molecular networking

Eleven undescribed guaiane-type sesquiterpenoids, named daphnegenols A-K (1–11) and a known analog (12) were targeted for isolation from the root of Daphne genkwa by LC-MS/MS-based molecular networking. Their diverse structures were elucidated through extensive spectroscopic methods, quantum chemical calculation and X-ray single crystal diffraction, including 5/7 bicycle, 5/6/7 tricycles and 5/6/5 tricycles guaiane-type sesquiterpenoid. Daphnegenol A (1) possessed a rare six membered oxyheterocyclic ring which was constructed by oxidation and cyclization at C-1 and C-11. The anti-acetylcholinesterase and anti-neuroinflammatory activities of compounds 1–12 were measured.     

F-对沸石分子筛双四元环影响的量子化学计算

采用PM3量子化学计算方法研究了沸石分子筛及无机微孔晶体结构中双四元环内含F^-及不含F^-的8种模型簇的几何结构、电子结构以及稳定性,考察了F^-对双四元环结构和性质的影响,发现F^-的存在依次增强了纯硅、磷铝和磷镓双四元环的稳定性,而降低了硅铝的稳定性,F^-在双四元环中所处位置的计算值与实验晶体数据基本吻合.     

Theoretical study on initial decomposition paths of energetic materials featuring RDX ring

The molecular properties of RDX are affected by the introduction of different functional groups, and the decomposition process of these analogues is studied in this paper. DFT method is used to study the initial decomposition reaction paths of 30 high energy materials based RDX skeleton. In the nitro cleavage reaction, the energy barrier become relatively low by introducing CH(NO₂)₂ or  C(NO₂)₃ groups on the C site of the six membered ring. In the ring opening reaction, the ring opening process is easier to proceed by introducing  NH₂ or  NHNH₂ groups on the C site of the six membered ring.     

On the effect of ring size in the cyclization of carbonyl and vinyl radicals onto alkenes

It is demonstrated that carbonyl and vinyl radicals cyclise readily onto alkynes when the product is a five membered ring but not when the product is a six membered ring; a transition state model is proposed to explain these observations.     

Relative reactivity of three and four membered rings--the absence of charge effect

Radical (neutral) and electrophilic (cationic) ring opening reactions were studied computationally in order to probe the difference in reactivity between three and four membered rings. Using the Marcus equation we have shown that the activation energy for the four membered ring opening is close to the Marcus predicted barrier whereas three membered rings display much higher reactivity than that predicted by the Marcus equation. Thus, the reactivity of the three membered rings is enhanced, in addition to the strain release, by another factor which is not operative in the four membered rings. It is clear also that this factor is not charge dependent. The possible origin of this effect is discussed.     

Silicon-guided rearrangement of 10-methyl-4,5-epoxydecalins. Methyl versus methylene migration

The Lewis acid-promoted rearrangement of two 10-methyl-4,5-epoxydecalins bearing a trimethylsilyl (TMS) group on C-1 or C-9 has been studied. Migration of the C-9 methylene group to C-5 is the major reaction pathway when the TMS and the oxirane groups are on the same ring while methyl migration results exclusively when they are on different rings.     

Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 2. Structures of catalyst‐alkoxyborane adduct with a four‐membered ring and succeeding reaction intermediates

Quantum chemical ab initio computations of the structures and properties of oxazaborolidine‐alkoxyborane adduct with a B? N? B? O four‐membered ring and succeeding reaction intermediates are carried out in the current work by means of the Hartree–Fock (HF) and the density functional methods. All the structures are optimized completely at the HF/6‐31G(d) and Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP)/6‐31G(d) levels. As shown in the obtained results, the oxazaborolidine‐alkoxyborane adduct with a B? N? B? O four‐membered ring may be formed during the reduction of the carbonyl bond of the catalyst‐borane‐keto oxime ether adduct. The breakdown of the B? N? B? O four‐membered ring results in the formation of the adduct with a B? N? B? O? C? C? N seven‐membered ring and an oxime bond. The reduction of the oxime bond leads to the adduct with a chiral oxime carbon. The B(2)? N_{C? N} bond in the B? N? B? O? C? C? N seven‐membered ring of the adduct with a reduced oxime bond is weaker comparatively and thus may be more easily broken down. All the adducts have four stable structures. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 294–306, 2003     

Total Synthesis of Talatisamine

Talatisamine ( 1 ) is a member of the C₁₉‐diterpenoid alkaloid family, and exhibits K⁺ channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5‐membered‐ring structure (ABCDEF‐ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6‐membered AE‐ring 7 and aromatic 6‐membered D‐ring 6 . AE‐ring 7 was constructed from 2‐cyclohexenone ( 8 ) through fusing an N‐ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7 , an oxidative dearomatization/Diels–Alder reaction sequence generated fused pentacycle 4 b . The newly formed 6/6‐membered ring system was then stereospecifically reorganized into the 7/5‐membered BC‐ring of 3 via a Wagner–Meerwein rearrangement. Finally, Hg(OAc)₂ induced an oxidative aza‐Prins cyclization of 2 , thereby forging the remaining 5‐membered F‐ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8 .     

Synthesis of aminopyrimidylindoles structurally related to meridianins

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ position.     

The schmidt reaction with oxa- and azabenzocycloalkenones

Five, seven and eight membered ring oxa- and azabenzocycloalkenones were submitted to the Schmidt reaction and the ratio of the respective isomeric rearrangement products have been determined and compared with that of six membered ring oxa- and azabenzocycloalkenones.     

Synthetic and Organocatalytic Studies of Quinidine Analogues with Ring‐Size Modifications in the Quinuclidine Moiety

Six highly enantiopure analogues of [2.2.2] were synthesized with five‐ or seven‐membered rings in the (original) quinuclidine skeleton. Five of these compounds were prepared through epoxide opening by a secondary cyclic amine, providing the nor‐ and homoquinuclidine moieties through five‐ and six‐membered ring formation. This method failed in the case of seven‐membered ring formation, so for that particular ring size a different synthetic route starting from 3‐quinuclidone was applied. The six novel analogues were examined as organocatalysts in four asymmetric conjugate addition reactions and the results compared with those of known cinchona alkaloid catalysts. This study shows that modification of the quinuclidine ring can have a substantial influence on catalyst activity and enantioselectivity. To acquire more insight into the characteristics of the new catalysts, the pK_aH values were determined by means of fluorescence spectroscopy. Furthermore, relative reaction rates of conjugate thiol additions reactions catalyzed by these quinidine analogues were measured through polarimetry.