Corioline

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

For his synthesis of the anti-tumour compound diketo-coriolin, Danishefsky needed (9) with its two fused five-membered rings, Enone disconnection suggests two possible precursors. 

H. Umezawa hoped to obtain immunostimulants from microbes, because, in cancer patients, the immune response is lowered. In 1972, H. Umezawa, T. Takeuchi, and M. Ishizuka (now Vice-Director of the Institute for Chemotherapy, a branch of IMC) found that the administration in mice of a small dose of diketocoriolin B, an oxidation derivative of the antitumor antibiotic coriolin B (1971), increases the number of mouse-spleen cells... 

These catalysts have been applied to D-A reactions that are parts of several important synthetic routes, thereby making them enantioselective.96 For example, key intermediates in the synthesis of cortisone and coriolin were prepared in enantiomeri-cally pure form using catalyst B. 

When the monotosylate (129) was treated with K2C03 in 60% aq. acetone in a sealed tube at 85 °C fo.r 1 day, the compound (130) was obtained as a single product. Compound (130) could be converted to ( )-hirsutene (131a) by further reactions 43). Furthermore, (130) could be also transformed to ( )-coriolin (131 b)44). 

Some illustrative examples from the field of polyquinanes are the synthesis of some derivatives of bicyclo[3.3.0]octane 6 (Scheme 6.7) [12] [15] -which have been used in the total syntheses of coriolin, hirsutic acid and quadrone- and the synthesis of triquinacene 7 and some of its derivatives. The retrosynthetic analysis of perhydrotriquinacene-l,4,7-trione (7a) is shown in Scheme 6.7bis. In the actual synthesis the hydroxy groups must be protected either as trialkylsilyl ethers or more conveniently as benzyl ethers [16] [17]. 

Khand annulations (extremely efficient in the synthesis of polyquinanes and cyclopentanoid sesquiterpenes -triquinacene, coriolin, etc.-, among many others). 

Chemical modification of coriolin B (55S) of rather extensive scope has teen described 334,33S) ... 

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

To arrive at racemic coriolin, Danishef sky and coworkers chose to add an acetonyl fragment to a bicyclic enedione by Diels-Alder chemistry (Scheme LXXIII) Treatment of the resulting adduct 695 sequentially with a series of conventional reagents produced the key intermediate 696. Suitable aldolization deUvered 697, the functionality in which was adjusted by deconjugation and reduction. Fiuther reduction of dPSiwith lithium in liquid ammonia and methanol followed by epoxidation afforded 699. Selective oxidation of the more accessible hydroxyl group and phenyl-sulfenylation gave 700 which experiences smooth elimination to 701 after conversion to the sulfoxide. As before, epoxidation completed the sequence. 

In a manner paralleling somewhat their strategy for carbaprostaglandin synthesis (Scheme LX), Ikegami, et al., have realized a coriolin total synthesis starting from 1,3-cyclooctadiene. With 701 in hand, they proceeded to elaborate the functionalized... 

Diketone 228, prepared by Mehta in conjunction with another study, has been transformed into 717 in a clever sequence of reactions which required no protection steps The conversion of methanoindene 718 into the highly functionalized intermediate 719 that might be serviceable as a coriolin precursor has been published... 

This unnatural acid is used as a chiral intermediate for the synthesis of a number of products. Chemical asymmetric synthesis was very difficult and so the stereoselective synthetic properties of enzymes were exploited to carry out a selective reduction reaction. The stereoselective hydrolysis of protein amino acid esters had already been commercialised by Tanabe in Japan using immobilised aminoacylase, and selective reduction reactions using whole yeast cells are already used in a number of processes, such as the selective reduction of the anti-cancer drag Coriolin. 

Diels-Alder reaction. The Diels-Alder reaction of 1 with 2 provides a key step in a total synthesis of alternative mode, the less stable trans-fusion ol the bicyclopcntanc system is formed. The product is converted in two steps into... 

The capnellene (1) of marine origin and derivative capnellenols such as 2 belong to the family of sesquiterpenes. Similar terpenes with a tricyclic [6.3.0.01undeeane skeleton are also found in plants, including such substances as hirsutene (3) and corioline (4). 3... 

The final step in Danishefsky s synthesis of the sesquiterpene coriolin (2)3 required bis epoxidation of 1. All attempts to effect this reaction in one step resulted in a mixture of the desired diepoxide (2) and epicoriolin (3) in about equal parts under best conditions. However, a two-step epoxidation procedure (1 >4 and 5 ->-6) resulted in a stereoselective synthesis of 2. 

Methyleneeyclopentane annelation (9,454-455). The mesylate (2) of 1 has been usedasan electrophilic equivalent of trimethylenemethane for methyleneeyclopentane annelation of a cyclopentanone in a synthesis of coriolin (7).2 Thus, reaction of the enolate of 4, a protected equivalent of 3, reacts with 2 to give 5, which after oxidation to the disulfone is cyclized by fluoride ion to the tricyclic methyleneeyclopentane derivative 6. The product is converted into 7 by several known transformations. 

Methylenecyclopentanes.2 Trost and Curran have used 1 as an electrophilic synthon for trimethylenemethane. Thus 1 reacts with the anion of 2 to give 3 in 72% yield. This product was oxidized to the disulfone, which was then cyclized to 4 by F. Various transformations are possible for the exocyclic methylene group. For the synthesis of coriolin (6), the group was converted to a pem-dimethyl group by cyclopropanation and hydrogenolysis. The product (5) was converted in several more steps into 6. 

These intramolecular meta-addition processes were utilized in the key steps for the total synthesis of a-cedrene [245], isocomene [246], hirsutene [247], coriolin [248], silphinene [249], rudmollin [250], laurenene [251], and fenestranes [252-254], which were synthesized by Wender s and Keese s groups (Scheme 58). 

The anti-cancer compound coriolin 23 has three fused five-membered rings and two epoxides. Notice that the 3/5 and both 5/5 ring fusions are cis. There have been many syntheses of coriolin, most using stereochemistry from folded precursors.7 We shall feature a couple of examples. Matsomoto s synthesis involves the hydroboration of alkene 24. The addition of borane is cis 25 and the boron is replaced by OH with retention of configuration to give 26. The hydroboration occurred on the outside of the molecule, on the same face as the ring junction hydrogens.8... 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

Curran s elegant approach to the natural products ( )-hypnophilin and ( )-coriolin is among the best examples of a Sml2-mediated sequence and consists of a 5-exo-trig cyclisation followed by a stereoselective 5-exo-dig cycli-sation in a radical-radical cascade (Chapter 7, Section 7.4).4 More recently, Kilburn employed a Sml2-mediated radical-radical sequence involving a methylenecyclopropyl ketone in the preparation of paeonilactone B.5,6 In... 

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