An Enantiospecific Formal Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone

An enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene fusicoauritone has been accomplished, starting from 5-isopropyl-2-methylcyclopent-1-enemethanol [available in three steps from (R)-dihydrolimonene] employing two ring-closing-metathesis reactions for the construction of the eight- and five-membered rings.

天然产物Standishinal 的首次全合成研究

具有1，1，4α-三甲基氢化芴骨架结构的天然三环二萜化合物自然界中不常见。在该类化合物中，Standishinal 具有良好的芳香化酶抑制活性和细胞毒活性。迄今未发现有Standishinal 的全合成报道，因此，我们对Standishinal 的全合成进行了探索，在该过程中得到以下实验结果： 1. 发现MSA/P2O5、MSA 在无溶剂条件下，25 °C 时烷氧基苯即可实现向苯酚的转化，但在CH3NO2 中，温度升高至80 °C 并未发生反应。 2. 烷氧基苯或对溴苯酚与α-环香叶酸在不同温度下以MSA/P2O5、MSA、PPA为催化剂以CH3NO2 为溶剂或以BF3·Et2O为催化剂时均不发生Friedel-Crafts酰化反应。 3. 对溴苯酚与香叶酸在p-TsOH 催化作用下发生了香叶酸向α-环香叶酸环化、α-环香叶酸环与对溴苯酚的酯化，得到了唯一产物α-环香叶酸对溴苯酯，产率68%。 Standishinal is one of tricyclic-diterpenes possessing the uncommon 1, 1,4a-trimethylhydrofluorene skeleton. Standishinal possesses cytotoxic and aromataseinhibitory activities. Till now, no synthesis of standishinal has been reported. Inattempt to synthesize standishinal, the following phenomenon were observed: 1. Alkyloxybenzenes could be transformed into corresponding phenol at 25 °C inthe presence of MSA/P2O5 or MSA under solvent free condition. ButAlkyloxybenzenes are stable in presence of MSA/P2O5 or MSA in CH3NO2 even at 80 °C. 2. Friedel-Crafts acylation of alkyloxybenzenes and p-bromophenol withα-cyclogeranic acid could not be realized under catalysis of MSA/P2O5, MSA or PPAin CH3NO2, or under catalysis of BF3·Et2O without CH3NO2. 3. The reaction of 4-bromaophenol and geranic acid in the presecnce of p-TsOHafforded 4-bromophenol α-cyclogeranoate in which cyclization of geranic acid toα-cyclogeranic acid was followed by esterification of α-cyclogeranic acid with p-bromophenol.

Enantiospecific approach to the tricyclic core structure of tricycloillicinone, ialibinones, and takaneones via ring-closing metathesis reaction

Enantiospecific synthesis of the tricyclic core structure present in the biologically active natural products tricycloillicinone, ialibinones, and takaneones, starting from the readily available campholenaldehyde employing a transannular RCM reaction as the key step, has been accomplished.

Syntheses of the trans,meso- and racemic C11 acids, degradation products of diterpene acids

Syntheses of the isomers of the C11 acid, 1(a),3(a)- dimethylcyclohexane-1 (e),2(e),3(e)-tricarboxylic acid (A) and 1(a),3(e)-dimethylcyclohexane-1(e),2(e),3(a)-tricarboxylic acid (B), the latter by two different routes, are reported. Two of the four possible isomers of the precursor triester, trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate, on individual methylation followed by hydrolysis, gave the trans,meso-acid (A), identified by comparison with an authentic sample, and the cis,trans-form (B) whose structure and configuration were proved by comparison with a specimen obtained by the unambiguous and highly stereoselective second synthesis. This demonstrated that methylation of the triester isomers occurs stereospecifically and exclusively at C-3. In the second sequence, it has been possible to assign definite conformations to four key intermediates and the final product, directly from n.m.r. spectra, from changes in these spectra accompanying specific steps, and from chemical evidence. Comparison of the n.m.r. spectra of the isomeric triesters (A) and (B) has provided unequivocal proof of the accepted trans,meso configuration for the abietic acid degradation product (A).

Enantiospecific synthesis of the tricyclic core structure of lippifolianes

An enantiospecific synthesis of the [6.6.3]-tricyclic carbon framework, 2,6,6,9-tetra-methyltricyclo[5.4.0.02,4]undecane, present in the sesquiterpenes lippifolianes and the diterpenes cyclosclareol, metasequoic acids and parguerols, starting from the readily available monoterpene (R)-carvone, is described.

Polyquinanes from (R)-(+)-limonene. Enantioselective total synthesis of the novel tricyclic sesquiterpene (-)-ceratopicanol

The first total synthesis of the biogenetically important and structurally novel triquinane sesquiterpene (-)-ceratopicanol has been accomplished.

An Enantiospecific Approach to the 5-8-5 Tricyclic System of Basmanes

An enantiospecific synthesis of the 5-8-5 tricyclic ring system present in the basmane diterpenes has been accomplished, starting from ethyl 3-isopropyl-2-methylene-1-methylcyclopentane-acetate readily available in five steps from (R)-limonene] employing an RCM reaction for the annulation of cyclooctane and an intramolecular rhodium carbenoid CH insertion reaction for the construction of the cyclopentane ring.

An approach toward the synthesis of PPAP natural product garsubellin A: construction of the tricyclic core

In a study directed toward the bioactive natural product garsubellin A, an expedient route to the bicyclo 3.3.1]nonan-9-one bearing tricyclic core, with a bridgehead anchored tetrahydrofuran ring, is delineated. The approach emanating from commercially available dimedone involved a DIBAL-H mediated retro aldol/re-aldol cyclization cascade and a PCC mediated oxidative cyclization as the key steps. (C) 2013 Elsevier Ltd. All rights reserved.

Palladium-catalyzed asymmetric allylic alkylation: insights, application toward cyclopentanoid and cycloheptanoid molecules, and the total synthesis of several daucane sesquiterpenes

The asymmetric construction of quaternary stereocenters is a topic of great interest in the organic chemistry community given their prevalence in natural products and biologically active molecules. Over the last decade, the Stoltz group has pursued the synthesis of this challenging motif via a palladium-catalyzed allylic alkylation using chiral phosphinooxazoline (PHOX) ligands. Recent results indicate that the alkylation of lactams and imides consistently proceeds with enantioselectivities substantially higher than any other substrate class previously examined in this system. This observation prompted exploration of the characteristics that distinguish these molecules as superior alkylation substrates, resulting in newfound insights and marked improvements in the allylic alkylation of carbocyclic compounds.

General routes to cyclopentanoid and cycloheptanoid core structures have been developed that incorporate the palladium-catalyzed allylic alkylation as a key transformation. The unique reactivity of α-quaternary vinylogous esters upon addition of hydride or organometallic reagents enables divergent access to γ-quaternary acylcyclopentenes or cycloheptenones through respective ring contraction or carbonyl transposition pathways. Derivatization of the resulting molecules provides a series of mono-, bi-, and tricyclic systems that can serve as valuable intermediates for the total synthesis of complex natural products.

The allylic alkylation and ring contraction methodology has been employed to prepare variably functionalized bicyclo[5.3.0]decane molecules and enables the enantioselective total syntheses of daucene, daucenal, epoxydaucenal B, and 14-p-anisoyloxydauc-4,8-diene. This route overcomes the challenge of accessing β-substituted acylcyclopentenes by employing a siloxyenone to effect the Grignard addition and ring opening in a single step. Subsequent ring-closing metathesis and aldol reactions form the hydroazulene core of these targets. Derivatization of a key enone intermediate allows access to either the daucane sesquiterpene or sphenobolane diterpene carbon skeletons, as well as other oxygenated scaffolds.