A-onocerin

Similarly, efficient tetracyclization (MeAlCl2-promoted) of the bis-allylic silane/ bis-epoxide 97 constitutes the key step in the synthesis of (+)-a-onocerin. In this case, because of the presence of the bis-allylic silane group, a double bis-annula-tion occurs, with the formation of the ethylene-bridge linked bis-decalin system present in the target compound (Scheme 8.26) [46],... 

A more complicated example, in which the presence of symmetry reduces the problem of creating eight chiral centres to only four, is the case of (+)-a-onocerine (8), the synthesis of which [15] was performed by coupling of the two enantiomerically pure C 5 units (7, X = COOH), with the correct stereochemistry, in order to prevent the formation of the unnatural meso form d,l + l,d) (Scheme 4.2). 

As part of the total synthesis of the triterpene (+)-a-onocerin, one of the first total syntheses in which RuO played a key role, a diphenylethyleneacetoxyketone was oxidised to the corresponding acetoxyketoacid by RuO /aq. Na(10yacetone. Aromatic ring oxidation was also involved (cf. 3.3.1 below) [219]. An oxidative cyclisation of a 1,5-diene to a diol by RuCl3/Na(10 )/wet SiO /THF formed part of the synthesis of the antitumour agent cw-solamin [220]. 

Using a similar process, (+)-a-onocerin 54, a known acetylcholinesterase inhibitor [32], was assembled by Corey and co-workers in only four steps starting from advanced acyclic intermediate 56 (Scheme 12.10) [33],... 

Scheme 12.10. Synthesis of a-onocerin using butyldimethylsilyl, THF = tetrahydrofuran, a three-component nucleophilic addition/Brook Tf = trifluoromethanesulfonyl, DME = 1,2-rearrangement/alkylation on acylsilanes, by dimethoxyethane, TMS = trimethylsilyl, Corey and co-workers [33]. TBS = t- TBAF = n-tetrabutylammonium fluoride.

One step in the production of (5), a key intermediate in a synthesis of the tetracyclic triterpene a-onocerin, involved allylic oxidation of the a,)3-unsaturated ester (1). This was accomplished with Se02 in boiling acetic acid.18b The unsaturated hydroxy lactone produced (2) was next to be converted into the saturated keto acid (5), presumably by a stepwise process. However, the Israeli investigators were pleas-... 

This drug group includes Cimicifugae rhizoma (Tetracyclic tritcrpene glycosides, actein, cimifiigosidc) and Ononidis radix (Triterpene a-onocerin = onocol). 

The coupling of carboxylic acids has been profitably used in natural product synthesis. Kolbe electrolysis of 8 is part of a (-j-)-a-onocerin synthesis [36], the electrolysis of 9 afforded a dimer with two quaternary carbon atoms [37], and 2,6,10,15,19,23-hexamethyltetracontane has been synthesized from 10 [38]. Cyclo-propylcarboxylic acids, e.g. 11 [39] and 12 [40], could be coupled to bicyclopropyl compounds others led to allylic compounds via ring opening of an intermediate carbenium ion. The dimerization of half-esters of diacids is also of industrial interest, because in this way l, -diesters are easily accessible [41]. 

Time studies with Heliantims amuiiis indicate the progressive oxidation of /j-amyrin (100) to echinocystic acid (lOl). The enzyme involved in the cyclization of 2,3 22,23-bisoxidosqualene to a-onocerin (102) has been partially purif.ed. ... 

Serratenediol 207 is a member of a recently discovered class of pentacyclic triterpenes,which have a seven-membered C ring and an entirely different skeletal structure from the triterpenoids described above. The compounds may be classified as a modified hopane group with a close biogenetic relationship, serratenediol being chemically interrelated with a-onocerin by a simple transformation. 

Lyaloside, lyaktsidic acid see Ophiorrbiza alkaloids. Lyclavatol see a-onocerin. 

After Stork etaL 123) had carried out the total synthesis of a a-onocerin (68), Tsuda and Hattori 124) in 1967 succeeded in converting (68) to hydroxyhopanone (69) via gammaceran-3-on-21-ol (70) (see Chart 16). 

A good example of the simplicity and power of the chemistry to rapidly construct complex systems is provided by the Kolbe dimerization of (55) as the key step of a total synthesis of the triterpene (-l-)-a-onocerin (57 Scheme 14) [33]. Thus, oxidation of (+)-hydroxy keto acid (55) in methanol containing a trace of sodium methoxide and at a temperature of 50 °C, followed by acylation and chromatography, provided (+)-diacetoxydione (56) in a 40% yield. 

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