Asteriscanolide synthesis

L 9. Kraffit, M.E. Cheung, Y.Y. Capucao, A.J. Synthesis of the First Inside-Outside Eight-Membered Ring via Ring-Closing Metathesis A Total synthesis of (+/-)- Asteriscanolide Synthesis 2000, 7, 1020-1026... 

Scheme 22 Efficient cyclooctene-forming diene-ene RCM, facilitated by cyclic constraint in Paquette s total synthesis of asteriscanolide (116) [75]...

The [4+ 4]-cycloaddition reaction of tethered bis-dienes has been used by Wender and co-workers in total synthesis as exemplified in syntheses of ( )-salsolene oxide and (-l-)-asteriscanolide (Scheme 28). In the synthesis of ( )-salsolene oxide, a nickel(0)-catalyst cleanly effects the cycloaddition of the two conjugated dienes in compound 93 to afford the bicyclo[5.3.1]undecadiene in a good yield and with moderate selectivity.99 The first synthesis of (-l-)-asteriscanolide was accomplished in only 13 steps. The key [4+ 4]-cycloaddition reaction efficiently set the requisite eight-membered ring of (-l-)-asteriscanolide in good yield and with excellent diastereoselectivity.100 The diastereoselective [4 + 4]-cycloaddition has also been applied to the synthesis of the core ring system found in several sesterterpenes such as the ophiobolins (Scheme 28).101... 

Regioselective singlet oxygen ene reactions have been also used, as key steps, towards the synthesis of (+)-asteriscanolide (167) , a-D-sorbofuranose (2S,3R,5R) (168) and a-D-fmctofuranose (2S,3S,5R) (169) ° (Scheme 62). 

Intermolecular PKR is not widely applied. Krafft and co-workers reported the synthesis of asteriscanolide. In their approach, regioslective intermolecular PKR with propene is used for the construction of the cyclopentane backbone of the target molecule (Equation (42)). ... 

The sesquiterpene (+)-asteriscanolide 1 was first isolated from Asteriscus aquaticus L and characterized by San Feliciano in 1985.1 It has captured the attention of organic chemists mainly because of its uncommon bicyclo[6.3.0]undecane ring system bridged by a butyrolactone fragment. The only prior enantioselective synthesis of 1 has been described by Wender in 1988 featuring an Ni(0)-promoted [4 + 4]-cycloaddition.2 Booker-Milburn and co-workers described the sequential application of intramolecular [2 + 2]-photocycloaddition, Curtius rearrangement, and oxidative fragmentation to produce the 7-desmethyl derivative in 1997.3... 

The preceding synthesis realized by Paquette provides (-i-)-asteriscanolide in 13 steps starting from protected 2-bromo-4,4-dimethylcyclopentenone (2) in an overall yield of 4 %. The key steps are the convergent merging of the readily available enantiopure cyclopentanone sulfoxide 3 and the methyl 4-hydroxybutynoate 14 This domino Michael-Michael addition with a heteronucleophile has... 

Asteriscanolide (65) is a cyclooctane sesquiterpene lactone that has been synthesised by a number of groups who have employed a variety of different strategies. In 2001, Krafft and co-workers developed a strategy that utilised the intermolecular PK reaction as a key step in its synthesis (63- 64 - Scheme 23).71... 

Scheme 23 Cyclopentenone formation in the total synthesis of ( )-asteriscanolide.

The nickel-mediated [4 + 4] cycloaddition strategy has also provided a concise and stereocontrolled route into the sequiterpene lactone (+)-asteriscanolide (128).The basic features of this approach are outlined in Scheme 17. The critical [4 + 4] cycloaddition step occurred under standard conditions to give the key intermediate in 67% yield. Clearly, the intramolecular version of the nickel-catalyzed diene cyclodimerization has been established as a powerful and highly-selective protocol for the synthesis of cyclooctane ring systems and should find extensive application to natural product synthesis. 

Another synthesis of asteriscanolide was completed at about the same time [35], this time introducing oxygen functionality early and during the assembly of the... 

A few applications of intramolecular Pauson-Khand reactions in organic synthesis have been reported. For example, total syntheses of asteriscanolide (Scheme 254) and cis-9-retinoic acid and tagretin analogs have been completed (Scheme 255). 

Zero-valent nickel is especially effective for the cyclization of (7j5(allyl) bromides.2 4 295 Corey used this technique to cyclize 450 to 451. Subsequent photolysis in the presence of diphenyl disulfide (PhSSPh) gave humulene, 452. 94 Wender et al. reported a novel [4+4]-cycloaddition reaction in which two diene moieties are coupled with a nickel(O) catalyst to form eight-membered rings. In Wender s synthesis of asteriscanolide,... 

Scheme 2. Synthesis of (4)-asteriscanolide via metal-catalyzed [444] cycloaddition.

An elegant use of [4]annulene chemistry utilizes the stable tricarbonylcyclobutadiene iron complex as a protected cyclobutadiene.One advantage over the aluminum cyclobutadiene complex is the ability of the tricarbonylcyclobutadiene iron complex to be amenable to synthetic modifications of the four-membered ring. Typically, ceric ammonium nitrate (CAN or other oxidants) may be used to oxidize the iron and liberate free cyclobutadiene. An example of this methodology is shown in Scheme 2, as applied to the synthesis of (-i-)-asteriscanolide. Further examples of reactions utilizing this chemistry are shown in Table 1. 

In the asymmetric synthesis of asteriscanolide, Wender et al. treated iso-buly-rate 9, obtained from the l,4-diene-3-ol, with LDA to get the enolate, which rearranged at 0 °C [27]. The resulting dienoic acid was converted to tetraene 10. Ni(0) mediated-[4-i-4]-cycloaddition of this tetraene gave the tricyclic lactone 11 which was converted to the sesquiterpene (-i-)-asteriscanoUde (Scheme 5.1.16). 

Similarly, the vinyUithiums 130 and 136, and the Hthiated cyclohexenic reagent 138 serve as useful building blocks for the synthesis of the macrocycHc diterpene antileukemic (it)-jatrophone (135) (1990JA8465), the sesquiterpenoid (+)-asteriscanolide (137) (2000JA2742), and the marine natural product nakienone B (139), respectively (Figure 5) (1996TL4679). 

This strategy has been successfully applied to the synthesis of (+)-asteriscanolide. Ring opening metathesis of the highly strained cyclobutene photoadduct 54 results in formation of the c/5-dialkenyl cyclobutane 55 with... 

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