Pseudolaric acid synthesis

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

In more recent work, Chiu and co-workers [167, 168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the di-polarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh2(OAc)4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13). The synthesis of 2-pyridones [169] and their application to the ipalbidine core [170] has been described. The pentacyclic skeleton of the aspidosperma alkaloids was prepared via the cycloaddition of a push-pull carbonyl ylide [171]. The dehydrovindorosine alkaloids 89 have also been investigated, in which the a-diazo-/ -ketoester 90 undergoes a facile cycloaddition to furnish 91 in... 

In a very recent example, Chiu and co-workers (84-86) used the tandem ylide-cycloaddition methodology to prepare advanced intermediates directed toward the synthesis of the pseudolaric acids. Pseudolaric acids are a family of diterpenes isolated from the root bark of Pseudolarix kaempferi. These novel compounds have shown antimicrobial activity comparable to that of amphotericin B and have demonstrated cyctotoxicity against several cancer cell lines (Fig. 4.5). 

It is worthy of note that this reaction is still the subject of solid and productive interest, as shown by the following recent examples. Chiu has exploited a rhodium carbene-promoted intramolecular formation of a carbonyl ylid - cycloaddition cascade as the key reaction in the synthesis of the nucleus of the cytotoxic diterpenoids pseudolaric acids A and B [54]. Although the diastereoselectivity was preferential for the undesired isomer 64, use of Hashimoto s chiral rhodium catalyst Rh2(SBPTV)4 reversed the selectivity in favor of 65 (64 65, 1 1.4) [55] (Scheme 29). 

Synthesis of pseudolaric acid A was carried out by Pan et al. [54] P-keto-ester compound 7-10, on treatment with iodo-compound 7-11, potassium carbonate and 18-crown-6 in toluene gave 7-12, which was hydrolyzed to compound 7-13 in dilute acetic acid. When the compound 7-13 was treated with 0.5 equivalent of potassium t-butoxide in THF-t-BuOH (1 1) at room temperature for 1 hr, the key compound 7-14 was obtained. The tin compound 7-15, after treatment of butyl lithium, reacted with 7-14 to form the diol 7-16. Reaction of 7-16 with sodium hydride gave the 8 -lactone 7-17 (Scheme 14). The remained steps are extension of the side chain and acetylation of the hydroxyl group at C-4 for accomplishment. 

In their studies towards the synthesis of polycyclic natural products such as pseudolaric acid A, Bai et al. reported the tandem Pummerer rearrangement and intramolecular [4 + 3] cycloaddition of sulfoxide 104." The reaction constitutes the overall [4 + 3] cycloaddition of a fully... 

Ylid trapping was used to establish the tricyclic system 8.529 in a synthesis of pseudolaric acid (Scheme 8.142), using a chiral rhodium complex to achieve better stereoselectivity in favour of the desired isomer. ... 

Enantioselective Synthesis of (—)-Pseudolaric Acid B via an intramoiecuiar [5-1-2] Cycioaddition Reaction of a Vinyicyciopropane with an Aikyne... 

Trost et al. reported the first asymmetric total synthesis of pseudolaric acid B by exploiting a rhodium-catalyzed intramolecular [5-1-2] cycloaddition reaction of a vinylcyclopropane with an alkyne (Scheme 8.2) [4]. The vinylcyclopropane having a tethered alkyne moiety 12 was synthesized from chiral precursors 9 and 11. Treatment of 12 with a cationic rhodium(1) catalyst promoted the [5-1-2] cycloaddition reaction to form a [5.3.0]bicyclic skeleton of 13 in a diastereoselective fashion. A few steps of functional group transformations provided the alkoxycarbonyl... 

SCHEME 19.46 Synthesis of a potential intermediate in the synthesis of pseudolaric acid A 210. 

A total synthesis of pseudolaric acid A was reported, featuring a Sml2-mediated intramolecular alkene-ketyl radical cyclization to generate the highly functionalized cyclopentane 141 (Scheme 25.67). ° When 140 was subjected to the annulation reaction in the presence of HMPA without... 

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