Cyclopentanoid natural products

Hirsutene (1) and A9(,2,-capnellcnc (2), the parent members of the hirsutane and capnellane families of triquinane natural products, respectively, are isomeric molecules that possess four contiguous stereogenic centers, one of which is quaternary. The linearly fused tricyclopentanoid frameworks of compounds 1 and 2 are obviously very similar, differing only with respect to the positions of the three methyl groups. An asset of Curran s tandem radical cyclization strategy is that it provides a unified entry into a wide variety of linear condensed cyclopentanoid natural products. As a result, it is possible to devise nearly identical retrosynthetic pathways for these structurally related molecules. 

Helmchen G., Goeke A., Kreisz S., Krotz A Lauer H., Linz G. Cyclopentanoid Natural Products Via Asymmetric Diels-Alder Reactions Stud. Nat. Prod. Chem. 1991 8 139-158... 

The synthesis of other angularly fused triquinanes as well as linearly fused sesquiterpenes such as hirsutene and capnellene quickly followed. Many general methods for the synthesis of cyclopentanoid natural products emerged as a result of the target-oriented effort [6]. These accomplishments have been reviewed extensively on numerous occasions [7]. This chapter reviews the history of retigeranic acid from its isolation and structure determination to published approaches to its synthesis and the four total syntheses accomplished to date. 

Besides the synthesis of racemic dehydroiridodiol [37], some ex-chiral-pool syntheses using (S)-limonene have been described [38]. Dehydroiridodial was synthesized in the same manner [39]. Since the increasing number of cyclopentanoid natural products and their interesting biological activity has stimulated considerable interest in the synthesis of such compounds, we have used our methodology to provide a new asymmetric synthesis of dehydroiridodial, dehydroiridodiol, as well as analogues [40]. 

The jasmonates are another class of disubstituted cyclopentanoid natural products very reminiscent of the prostaglandins. To efficiently assemble their main skeleton, Yamamoto and co-workers developed a clever three-component reaction methodology that was demonstrated by the total synthesis of both trans- and cis-methyl jasmonates 36 and 37 (Scheme 12.7) [25],... 

Access to (Z)-vinyl bromides allowed an efficient cyclopentenone synthesis and their application to the formation of cyclopentanoid natural products such as rosaprostol or a selective cox-2 inhibitor [63] (Eq. 47). 

Generation of the endocyclic double bond of cyclopentanoids has been accomplished frequently by rDA reaction of the appropriate cyclopentadiene. FVP has been used as the last step of the synthesis of the antibiotic ( )-pentenomycin (53) in 50% yield. " Other cyclopentanoid natural products that are synthesized by procedures based upon a nearly quantitative rDA reaction are jasmone (54) and alkyne (55), a precursor to methyl jasmonate. This same procedure has been applied to the synthesis of intermediates of prostaglandins such as (56). ... 

A very powerful and elegant methodology intensely developed in recent years for the construction of five-membered ring systems, e.g. of cyclopentanoid natural products, is based on the in situ formation of highly reactive Cj intermediates from a variety of synthetic precursors. These intermediates 1 can then serve as three-earbon, 2n-electron (Y = Hj) or 4 -electron (Y = CH, O) components in cycloaddition reactions, specifically of the [3-1-2] type, with various carbon-carbon - or carbon-heteroatom multiple bonds as 2rt-components. 

The development of syntheses for highly functionalized cyclopentanes has been enhanced by the isolation of numerous cyclopentanoid natural products. 4-Methylene-1-cyclopentenes (67) are interesting and versatile building blocks for such species. The preparation of these cyclopentenes has been accomplished by a three-step synthesis, the last of which is rDA cycloreversion under FVP conditions (equation 35). liiis final rDA step simply involves distillation of the adducts (66a-h), which yields cyclopentenes (67a-h) in a virtually pure state. 

Vinylcyclopropane-cyclopentene rearrangement (VCP-CP) reaction under thermal conditions is a useful transformation and has been extensively utilized in the synthesis of number of cyclopentanoid natural products.However, cw-alkyl-vinylcyclopropanes pose a serious problem since the retro-ene reaction, a lower energy pathway occurs readily instead. To obviate this problem, we sought to explore the excited state chemistry of c/s-alkyl-vinylcyclopropanes.t ] Thus, sensitized photolysis of (+)-A -carene readily afforded the VCP-CP product exclusively in a preparative yield. The obtention of a racemic product can be rationalized by involving a diradical intermediate.l l... 

Saturated and unsaturated products obtained via intramolecular hydrocarbonylation are precursors for cyclopentanoid natural products such as ( + )-(a)-cuparenone, laurene or acorane systems 14-16 18. The method is also applicable to heterofunctionalized 1,4-dienes giving cy-clopentanones with various additional functional groups20-21. 

Due to the growing interest in cyclopentanoid natural product synthesis, numerous methods for the construction of carbocyclic five-membered rings have been developed1- 4. Among these, [3 + 2] cycloaddition methodologies play a prominent role. 

G. H. Lauer, G. Linz, Cyclopentanoid Natural Products via Asymmetric Diels-Alder Reactions in Studies in Natural Products Chemistry (Ed. Atta-ur-Rahman), Vol. 8, Elsevier, Amsterdam, 1991, pp. 139-158. 

A salient feature of 4 is its ability to undergo monosaponification to the monoacid 5 in good yield. The presence of free acid and ester groups in the same substrate allows independent functionalization of each chiral carbon. Chiral hydroxylated cyclopentanes are of general interest as building blocks for the synthesis of cyclopentanoid natural products. Conversion of... 

Tsuji and his group have developed a palladium catalyzed cyclization reaction that has led to a simple synthesis of 2-carbomethoxy-3-vinylcyclopentanone 142, which they have utilized in syntheses of cyclopentanoid natural products. In the steroid field, 142 served as a ring D component in an orthoquinodimethane-based route to ( )-18-hydroxyestrone. The (-I-)-diastereomer is a component of pregnancy urine. ( )-Estradiol-3-methyl ether was also obtained (Scheme 19). ... 

Hehnchen G, Goeke A et al (1991) Cyclopentanoid natural products via asymmetric Diels-Alder reactions. Stud Nat Prod Chem 8 139-158... 

The radical cyclization products derived from sugars are useful for the synthesis of cyclopentanoid natural products. For example, the unprecedented 1,5-trans stereochemistry seen in the case of 4,6-0-benzylidene-glucose-derived radicals can be used to prepare optically active prostaglandin intermediates such as Corey lactone 44 (Fig. 7.12) [23]. 

The classic Kolbe synthesis has been used in recent years in an elegant manner by Schaeffer to prepare a number of natural materials such as the beetle pheromone, 88 ( fO). In a two-electron reaction which takes place through a rearrangement as shown in Fig. 7, 8 was converted to 3 which was used for the synthesis of several interesting cyclopentanoid natural products (fjl). A similar two-electron reaction not involving a rearrangement, led from to 5 ( 8). No stereochemistry is implied in and 5. 

The groups of de Meijere and Kostikov utilized the Bamford-Stevens reaction whilst demonstrating the dirhodium(II) tetraacetate catalyzed (chlorovinyl)cyclopropanation of enol ethers and dienol ethers. The resulting vinylcyclopropanes 17 play an important role as precursors to cyclopentenes en route to cyclopentanoid natural products."... 

M. Demuth and K. Schaffner, Tricyclo[3.3.0.0 ]octan-3-ones Photo-chemically Prepared Building Blocks for Enantiospecific Total Synthesis of Cyclopentanoid Natural Products , Angew. Chem., Int. Ed. Engl., 1982, 21, 820. 

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