Tetracyclic alcohols

One of the first uses of the allylic sulfoxide-sulfenate interconversion was made by Jones and coworkers64, who reported exclusive suprafacial rearrangement of the allyl group in the steroidal sulfoxide 17 shown in equation 13. Two other examples are shown in equations 1465 and 1566. Evans and coworkers have demonstrated the utility of the suprafacial allylic sulfoxide-sulfenate rearrangement in a new synthesis of the tetracyclic alcohol 24 (equation 16)67, as well as in a synthesis of prostaglandin intermediates as shown in equation 1768. The stereospecific rearrangement of the unstable sulfenate intermediate obtained from the cis diol 25 indicates the suprafacial nature of this process. 

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

Next step is the construction of 8- and 15-membered ring systems by sequential RCM [7]. Tetracyclic alcohol 13 was converted to 14 by sequential oxidation and Peterson olefination followed by deprotection of the TMS group. After protection of the amine with a Boc group, the imide carbonyl group was... 

Methylsterols (4-desmethyl triterpenes) and sterols (4,4-di-desmethyl triterpenes) present in olive oils are derived from the tetracyclic alcohols. The following methyl sterols (4a-methyl-7-cholesten-3p-ol compounds) are present 24-methylene, 24-methyl-, 24-ethylidene, and 24-ethyl. 

We thank Thorsten Dieckmann (EMBL, Heidelberg) for his help with confirming the structure of tetracyclic alcohol by HOHAHA-spectnim (TOCSY) with 15 ms/ 37 ms mixing and CH-correlation. 

Among the many other cyclic secondary alcohols that have been obtained by lipase-catalyzed enantiomer-selective acylation with high enantiomeric excess are aminofunctionalized cycloalkanols (40, 45-62, 75), bicyclo[3.3.0]octanols (78, 84-86), different types of tri- and tetracyclic alcohols (96-104), substituted indanols (87-94,123), hydroxy lactams (106,109-112) and brominated cyclohexenol derivatives (74, 77,124-127) (Table 11.1-21). 

The acid-catalysed cyclization of labdanes has continued to attract attention. The influence of a C-15 carbonyl group, as in (15), leads to compounds of the pimarane series (16) and to the enol-ether (17) rather than isoagathic acid derivatives even in the presence of formic acid. The tetracyclic alcohol (20) has been obtained by dehydration of sclareol (18) with perchloric acid. It is presumably formed via the carbocation (19). 

Toward this end, exposure (9 h) of dienophile (284) to 5.0 equiv. of dienoic acid (285) in 3.0 M LiClOr-diethyl ether gave rise in 72% yield to crystalline keto acid (286), a which was reduction with sodium borohydride in methanol at 0°C by treatment with concentrated hydrochloric acid afforded the crystalline tetracyclic alcohol (287). To set the stage for the inversion of configuration at C(9), tetracyclic alcohol (287) was transformed into tetracyclic enone (291), via tetracyclic ketone (290), which was readily available by a five-step sequence from (287) described above [133],... 

The synthesis of glaucarubolone described above commences with the tetracyclic alcohol (319), which we had prepared in conjunction with a synthesis of chaparrinone (226). The transformation of (319) into glaucarubolone requires (a) incorporation of a 2-oxo-A3,4 olefin unit into ring A, (b) elaboration of the C(8), C(ll) bridged hemiketal structural array in ring C, and (c) introduction of a C(15) p-hydroxyl group into the eventual ring D 8-lactone. 

A full report of the approaches to the synthesis of (CH)5 carbocations has been published.8 4 The carbocations were synthesized to study the suggestion that the most stable structure for such species was the pyramidal structure (8).8 Hart and Kuzuya8 approached the problem by the synthesis of the tetracyclic alcohols... 

The cyclization of manool to 14a-hibyl formate has been shown to proceed through a cyclo-octenyl cation (85) and thence to a tetracyclic intermediate (86) which would ultimately give the hibyl ester (87). The corresponding tetracyclic alcohols have been synthesized and shown to be converted into the 14-hibyl acetate. 

Wiesner carried out pioneering studies on the photocycloaddtion of vinylogous imides in the 1960s, and he first applied the intramolecular photochemical [2 + 2] enone-olefin cycloaddition reaction in natural product synthesis. In his landmark synthesis of 12-e/>i-lycopodine, compound 186 is irradiated to give a 70% yield of photoadduct 187. Protection of the ketone, epoxidation of the exocyclic double bond, and reduction of the epoxide give ketal alcohol 188. Deprotection of the ketal and spontaneous refro-aldol fragmentation lead to the diketone 190. Of note is that the bond cleaved in this retro-a do pathway (i.e., 189 to 190) is different from that of typical de Mayo reactions. Diketone 190 transforms to the tetracyclic alcohol 191 via aldol reaction, and this alcohol is converted to 12-e/7/-lycopodine in four steps. 

The carbocation (53), formed under super-acid conditions from the phenyl-substituted tetracyclic alcohol (50), appears to be destabilized relative to (52), formed from (49) under similar conditions. Thus, for example, (53) could only be formed from (50) in FSO3H-SO2CIF at below — 100 "C, whereas (52) can be studied at — 50 °C. Above that temperature rearrangement occurs to give a pair of bicyclo-[3,3,0]octyl allylic cations. Shift data on (53) indicate that the methyl-bearing carbon aioms at the base of the pyramid are more electron deficient than their counterparts... 

The irradiation of the less stable isomer 29a brought about a conformationally specific 1,7-hydrogen abstraction to give the tetracyclic alcohol 30 the stable 29P did not lead to the corresponding 31 but did... 

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