Tetracyclic lactone

Soon after the disclosure of the total synthesis of ( )-gingkolide B, (see ref. 8a) Corey reported a concise, enantioselective synthesis of tetracyclic lactone 23, see Corey, E. J. Gavai, A. V. Tetrahedron Lett. 1988, 29, 3201. Thus, in principle, gingkolide B could be synthesized in its naturally occurring enantiomeric form. 

As shown by Sato et al. N-phthaloyl derivatives of C-unprotected amino acids efficiently undergo decarboxylation upon irradiation [248,249]. In this case, the iV-phthaloyl a-amino acid of methionine 310 represents an exception, because the normal decarboxylation route is not followed. Two main products are obtained, the trans-hydroxy acid 313 and the tetracyclic lactone 314 [250, 251]... 

Each alkaloid has also been characterized by its UV-, IR-, and NMR-spectrum. This information together with some degradative work permits the recognition of the three classes of alkaloids listed in Table I (1) tetracyclic lactones, (2) highly oxygenated hexacyclic esters, and (3) one hexacyclic and two pentacyclic bases of low oxygen content. Several alkaloids, as yet unclassifiable, are collected in the inevitable miscellaneous group. 

The first asymmetric total synthesis of the hasubanan alkaloid (+)-cepharamine was completed by A.G. Schultz et al. In order to construct the c/s-fused A/-methylpyrrolidine ring, the advanced tetracyclic lactone was first converted to the primary carboxamide by treatment with sodium amide in liquid ammonia. Next the Hofmann rearrangement was induced with sodium hypobromite in methanol initially affording the isocyanate, which upon reacting with the free secondary alcohol intramolecularly gave the corresponding cyclic carbamate in excellent yield. 

A diastereoselective epoxidation of a tetrasubstituted double bond was accomplished with mCPBA in the total synthesis of (-)-21-isopentenylpaxilline by A.B. Smith et al." The tetracyclic lactone substrate containing the tetrasubstituted double bond was exposed to mCPBA in toluene at room temperature. The reaction mixture also contained sodium bicarbonate to neutralize the by-product m-chloro benzoic acid. The epoxidation exclusively took place from the less hindered a-face of the molecule. At a later stage, this epoxide was converted to the y-hydroxy enone moiety present in the natural product. 

Hydroxycyclopent-2-enones rearrange to diastereoisomeric mixtures of 2-oxa-bicyclo[3.1.0]hexan-3-onesin low yields if the alcohol function at C5 is secondary.17 In contrast, the tetracyclic lactone 4 is obtained in 70% yield upon sunlight irradiation of the... 

The total synthesis of (136) described for Grieco et al [144] commences with the tetracyclic lactone (361), which possesses all the carbon atoms of 14P,15P-dihydroxyklaineanone. Transformation of (361) into (136) requires elaboration of the 1 P-hydroxy-2-oxo-A3 4... 

Similarly, propargylic 3-indoleacetates 206, when treated with PtCl2, undergo an intramolecular [3+2] cycloaddition across the 2,3-indole bond to form the tetracyclic lactones 207 in excellent yields. This methodology (conversion of 208 to 209) has been successfully applied to the development of a short synthesis of the tetracyclic core of vindolinine (211) (Scheme 57). 

During an attempted conversion of blennin A (11.26) into vellerolactone (11.6), it was observed that upon exposure to DBU the lactarane skeleton of methanesulphonate 11.48 rearranged to the tetracyclic lactone 13.1. The suggested mechanism of this reaction is shown in Scheme 17 (705). 

The propargyhc esters 33 of (fS-indolyl)acetic acid undergo Au(I)/Ag(I)-catalyzed isomerization to the tetracyclic lactone 34, which is interpreted as a tandem (3,3)-sigmatropic oxa-CopE rearrangement followed by an intramolecular (2 + 2)-cydoaddition [155] ... 

The tetracyclic lactone quadrone (43) is a compound that has attracted the attentions and aspirations of many synthetic chemists in recent years. The molecule is a fungal metabolite from Aspergillus terreus which is found to exhibit antitumour activity. The critical step in a synthesis of quadrone that has been described by Burke et al is the regiospecific intramolecular Michael reaction of (41), in the presence of two equivalents of morpholine and a catalytic amount of toluene -sulphonic acid (p-TSA) in hot benzene, to produce the bicyclic dional (42). Interestingly, treatment of (41) with titanium tetrachloride instead led to the spiro-compound (44) as the sole isolable product, and the dienone (45) was the major product when (41) was heated under reflux in benzene in the presence of toluene-p-sulphonic acid alone. 

Pattenden et al. applied his expertise in polycyclic ring constructions based on radical-mediated cyclizations of polyolefin selenyl esters for the total synthesis of cytotoxic ( )-spongian-16-one, isolated from both New Zealand and Australian specimens of the sponge Chelonaplysilla viola-cea (Scheme 25.38). Treatment of selenoester 85 with Bu3SnH led to tetracycle lactone 86, which after methyle-nation gave the corresponding exocyclic methylene (not shown) in 42% overall yield. 

Griesbeck and co-workers further investigated PET reactions of sulfur-containing proteinogenic and non-proteinogenic amino acids and discovered an unusual solvent dependence of the product composition. Even more remarkable was the photochemical behavior of phthaloyl L-methionine 18 irradiation in acetone gave the tetracyclic lactone 20 in 72% yield (Scheme 6). In this particular case, PET oxidation at sulfur proceeds faster than a-decarboxylation vide infra). 

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