Quassinoids oxidation

Nakata showed that stoich. RuOyCCl oxidised steroidal diols to the corresponding ketones [237] electrogenerated RuO from RuO /aq. NaCl/Na(H3PO ) pH 4/ Pt electrodes converted diols to lactones and keto acids (Tables 2.1-2.4) [267] and RuCyaq. 10(0H)3/CC1 -CH3CN oxidised 3-(benzyloxy)-l,2-octanediol to the acid (Tables 3.4, 3.5) [107]. A diol was converted to a lactone by stoicheio-metric oxidation with RuOyCCl as part of the total synthesis of the quassinoid ( )-amarolide [82],... 

A diol was converted to a lactone by oxidation with stoich. RuOyCCl as part of the total synthesis of the quassinoid ( )-amaroMe [355] stoich. (PPh )[Ru(0)2Cl3]/... 

Manganese triacetate has been specifically reported as a reagent for a -oxidation.Mechanistic dualism analogous to LTA (vide supra) is observed, although the radical process may be more dominant. Watt and coworkers used this technique during the synthesis of quassinoids. Enone (113) was con-... 

Secondary positions tend to be more reactive towards oxidation than tertiary positions, unless steric hindrance (Uctates otherwise. Good examples of this are the chromic acid oxidation of the ether (12)4 and the ruthenium tetroxide oxidation of the ether (13), both of which lead to lactone formation (Scheme 2). Oxidation of the quassinoid intermediate (14), on the other hand, is completely nonselective (equation 15). ... 

Quassinoids.—Simarolide (136) had previously been the only substance providing a structural link between limonoids and quassinoids. The related picrasin A (137) has now been isolated from Picrasma quassioides P. ailan-thoides). It was accompanied in the extract by picrasin B (138) which was converted to quassin (139) by bismuth oxide oxidation and methylation. A series of closely related quassin derivatives, nigakilactones A (140), B (141), C (142), E (143), and F (144) occur with quassin in P. ailanthoides. - The structure of amarolide has been revised to (145). Observation of a large coupling between H-9 and H-11 in the n.m.r. spectrum makes the previous... 

Thus, the lactonisation through the C-17 hydroxyl leads first to C25 skeleton quassinoid, while lactonisation through the hydroxyl at C-21 and subsequent oxidation of the residual C-17 hydroxyl may result in second C25 skeleton quassinoid. 

From the structure-activity relationships discussed among quassinoids, it has been reported that the partial structures of the Cl-OH, C12-OH, 2-keto-3-ene and oxide-bridge are essential features for antileukemic activity. In this continuing series of studies on cytotoxic compounds of E. longifolia, two unique squalene-type triterpenes, characterized by eight asymmetric carbons and two or three tetrahydrofuran rings, were isolated from the woods of E. longifolia. While one of them was identified as the marine meso-triterpene ether, teurilene (43), the other was found to be a new compound, named eurylene (44), whose relative structure was... 

In a later study, a tetracyclic quassinoid skeleton was synthesized in optically active form, starting from (+)-methylcarvone. The sulfolene aldehyde (229) was prepared by regioselective allylation of 3-methyl-3-sulfolene, followed by oxidative cleavage of the alkene bond. Reaction of (229) with the enolate formed from methylcarvone (230) provided alcohol (231), which was acetylated to give (232). Heating (232) provided the tricycle (233) as a single diastereoisomer, and this was... 

Quassinoids are natural products formed by oxidative degradation of triterpene derivatives their biosynthetic precursors are similar to those of limonoids but the biosynthetic pathways of quassinoids have not been established so far [1]. At least 351 different natural quassinoids have been described in the literature (Fig. 125.1), and a large number of semisynthetic and synthetic analogues have been prepared for synthesis or medicinal chemistry purposes, mostly in last 30 years [see, for example, 2-4]. Several base skeletons have been described in the literature, and these can be classified into five distinct groups according to the number of atoms of the main chain (Fig. 125.1). 

No compounds with rings C and D opened, or with a 12-keto group and a lactone ring D, are known. It has been pointed out 81) that a 12-keto ring D lactone would be susceptible to reversed aldol reaction with loss of P-furfuraldehyde to give a quassinoid, and that this may well be the origin of quassinoids in nature. The similarity in ring A oxidation levels between nimbin and many quassinoids lends support to this view. 

The bruceolide esters are the only quassinoids which do not haive oxygenated functions at positions 1 and 2 but at 2 and 3. They have a diosphenol group at these positions and, in ring C, the hydroxymethyl at C-8 forms an oxide bridge to C-13. 

The synthetic technique is summarized in Scheme 3. Reaction of chaparrin (41b) with tert-butyldimethylsilyl chloride 11) afforded the crystalline disilyl derivative (93). The latter was obtained in better yield by silylation of (41b) with tert-butyldimethylsilyl enol ether of pentane-2,4-dione 105). The hydroxyl function at C-1 of (93) was effectively protected using trimethylsilyl triflate to afford the trisilyl lactone (94) which upon treatment with lithium diisopropylamide (LDA) and subsequent exposure to MoOs-pyridine-HMPA (M0O5PH) 104) gave the required 15-hydroxy lactone (95). Treatment of the latter with isovaleryl chloride afforded the crystalline ester (96) which was selectively desilylated to (97). Oxidation of the free allylic hydroxyl and complete desilylation of the resulting disilyl enone with tetrabutylammonium fluoride (BU4NF) afforded the natural cytotoxic quassinoid castelanone (34). 

Simaroubaceae. Specialization of quassinoid skeletons is accompanied by a West-East spacial radiation of the simaroubaceous lineage. Indeed the transition fi om American and West Afiican genera to East Afiican and Asian genera is accompanied by diversification of oxygenation and unsaturation patterns, as well as by increase in oxidation level of the quassinoids (P). 

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