Subject pentacyclic

Given our earlier success in epoxidizing the epoxy pentacycle 67 having the p-Cl-OH [see Scheme 14], the pentacycle 75 was subjected to directed reduction using NMe4B(OAc)3H in AcOH to give exclusively diol 82 in 94% yield with P-C1-OH [Scheme 19].61... 

An interesting example of the transfer of center chirality to helicity is the work by Ogawa et al., based on an asymmetric aromatic oxy-Cope rearrangement to provide nonracemic [5]helicenes (Fig. 15.8) [75]. The starting material with center chirality, bicyclo[2,2,2]ketone (-)-21 (>98% ee), was obtained by enzymatic resolution. In the annelation step, the phenanthrene derivative was subjected to aromatic oxy-Cope rearrangement, to afford a pentacyclic product in 47 % yield. The corresponding [5]helicene 22 was obtained in 7 % overall yield (> 98 % ee) after six steps. 

The Aspidosperma family of indole alkaloids has inspired many synthetic strategies for the construction of their pentacyclic framework of the parent compound aspidospermidine (366), since the initial clinical success of two derivatives, vinblastine (10) and vincristine, as anticancer agents. The alkaloids such as (-)-rhazinal (369) and (-)-rhazinilam (6) have been identified as novel leads for the development of new generation anticancer agents [10,11]. Bis-lactams (-)-leucunolam (370) and (-t-)-epi-leucunolam (371) have bio-genetic and structural relationships with these compounds [236]. Recently, enantioselective or racemic total syntheses of some of the these natural product were achieved. One successful synthesis was the preparation of the tricyclic ketone 365, an advanced intermediate in the synthesis of aspidospermidine (366), from pyrrole (1) (Scheme 76) [14]. The key step is the construction of the indolizidine 360, which represents the first example of the equivalent intramolecular Michael addition process [14,237,238]. The DIBAL-H mediated reduction product was subject to mesylation under the Crossland-... 

Manzamine alkaloids have been the subject of numerous synthetic studies owing to their novel molecular structure coupled with promising biological properties. Most of the synthetic studies on manzamine alkaloids focused on the construction of the ABCDE pentacyclic lower half of the manzamine structure. 

Later, this cycloaddition reaction was improved by the pretreatment of the enamide ester with an equimoler amount of trialkylsilyl trifluoromethanesul-fonate and triethylamine at ambient temperature. The synthesis of tyro-phorine (119) was achieved by the above improved method (Scheme 55). The enamide ester 441 was subjected to annulation using t-butyldimethylsilyl triflate and triethylamine at 15°C to produce the bicyclic lactam 442 in 68% yield. Oxidation of 442 with thallium(III) trifluoroacetate and boron triflu-oroetherate in a mixture of dichloromethane and trifluoroacetic acid at 4°C produced (83%) the pentacyclic compound 443. Hydrolysis of 443, followed by decarboxylation of the resultant acid, gave the pentacyclic lactam 444. Reduction of 444 with sodium bis(2-methoxyethoxy)aluminum hydride in refluxing dioxane afforded tyrophorine (119) (85CC1159). 

During the total synthesis of the pentacyclic sesquiterpene dilactone (+)-merrilactone A by S.J. Danishefsky et al., a two-carbon unit was introduced at C9 by a Johnson-Claisen rearrangement. This high yielding transformation was carried out in the presence of catalytic 2,2-dimethyl propanoic acid at 135 °C using mesitylene as the solvent. A mixture of diastereomeric esters were formed, which were later hydrolyzed and subjected to iodolactonization to form the second lactone ring present in merrilactone A. The natural product was synthesized in 20 steps with an overall yield of 10.7%. 

Following their recent synthesis of ( )-vincadifformine (Scheme 75) (343,344), Szantay and his collaborators have contributed another s3mthesis of pseudovincadifformine and its epimers (392). Condensation of the trypt-amine derivative 587 with the aldehydoester 698 gave, via an unstable secodine derivative, the epimeric tetracyclic esters 715, which, without separation, were subjected to debenzylation, with partial epimerization and cyclization. The product, a mixture of the two cis C/D-fused pentacyclic... 

In another approach, the transfer of homophthalate derived C-2 fragment of 14a/ 14b and 16a/16b in their acetic acid-catalyzed reactions with tryptamine gave mixtures of Z/E isomers of 107, which on HC1 treatment formed diastereomeric mixture of /i-carboline derivatives 108. Triethylamine/acetic acid treatment of 108 provided pentacyclic products 109a and 109b that have been subjected to some chemical modifications (85T3355). 

Yu et al. reported the synthesis of Na-methyl-16-ep/-pericychvine (180) (Scheme 5). The pentacyclic ketone 181 (which was obtained from D-(4-)-tryptophan methyl ester (156) similarly, and is described in Schemes 2 and 3) was subjected to a Wittig reaction, followed by hydrolysis to... 

The Brummond research group also illustrated that the stereoselectivity of these reactions can be controlled by tethering the first dienophile to the dendralene [22, 23]. In one such example, ester 84 underwent an e do-selective intramolecular DA reaction to provide the tricyclic diene 85 (Scheme 12.17). In this reaction, the dienophile is constrained to the bottom face of the molecule, thus controlling the it-diastereofacial selectivity of the cycloaddition. Piperidine 85 was then subjected to an ewdo-selective intermolecular DA reaction with NPhM to provide the pentacycle 86 in excellent yield. 

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