Of pseudopterosins

A recent example demonstrates that corals rely on induced biosynthesis of terpenes as a dynamic defense strategy as well. The induction of terpenoid secondary metabolites was observed in the sea whip Pseudopterogorgia elisabethae [162]. Levels of pseudopterosins 89-92, a group of diterpene glycosides with anti-inflammatory and analgesic properties (Scheme 23) [163-165], are increased in response predation by the mollusk Cyphoma gibbosum. First bioassays indicate that these natural products are involved in the chemical defense. 

Kocienski, P. J. Pontiroli, A. Qun, L. Enan-tiospecific syntheses of pseudopterosin agly-cones. Part 2. Synthesis of pseudopterosin K-L aglycone and pseudopterosin A-F agly-cone via a B-BA-BAC annulation strategy. 

Further studies on the synthesis of pseudopterosin A have been published recently L. Eklund, I. Sarvary and T. Frejd, J. Chem. Soc., Perkin. Trans. 1,1996, 303. 

Epoxy-ene cyclizations have been used as key steps in natural products synthesis. The preparations of pseudopterosin, a potent antiflammatory agent and analgesic <88JOCl584>, and (+)-aphidicolin <85TL6147,88JOC4929), (+ )-9,10-jyn- and (+)-9,10-an/i-copalol <92JOC4598> are representative examples of the synthetic utility of Lewis acid-catalyzed epoxide cyclizations. 

As pseudopterosins have proven to have a wide range of medical applications and while natural reserves are limited, extensive research was carried out towards their synthesis. Harrowven and coworkers [14] established an efficient synthesis of the tricyclic carbon skeleton. Two other research groups led by Corey [15] and Broka [16] developed a total enantiospecific synthesis of pseudopterosins. Broka and coworkers. 

From a taxonomically distinct and still unidentified specie of the Pseudopterogorgia genus, a related series of pseudopterosins containing bicyclic diterpenoid glycosides, 7 seco A-D, were also isolated and their structures elucidated by Look and Fenical [18]. Compounds 7 seco A-D possess potent anti-inflammatory and analgesic activities that are similar to the pseudopterosins, and also show antimicrobial activity towards the bacteria. Staphylococcus aureus. For example 7 seco-A, pseudopterosin exhibited a 69% reduction of inflammation in the mouse ear edema assay at a minimum inhibitory concentration (MIC) of 50 pg/ear. 

We presented a review of the natural product chemistry found in species of Pseudopterogorgia. These metabolites function as predator deterents and some of them proved to be (potential) therapeutic agents. The discovery of pseudopterosins and their potent anti-inflammatory activity should be especially highlighted as one of the most prominent (marine chemistry) scientific inventions of the last decade. We feel that the combination of the discoveries reviewed herein combined with drug design based on structure activity studies of these compounds will lead to therapeutic agents which although derived from marine life chemistry, will not rely on it as a source. 

In a series of publications, Nicolaou and coworkers have demonstrated the utility of DMP for the selective oxidation of 4-substituted anilides 894 to p-quinones 895 and 2-substituted anilides 896 to < -azaquinones 897 (Scheme 3.360) [1289-1291], The first process was applied to the short, efficient total synthesis of epoxyquinomycin B [1290], while the second type of oxidation allowed rapid access to complex analogs of pseudopterosin and elisabethin natural products [1291],... 

Corey et al. reported a successful total synthesis of pseudopterosin E (116) through a crucial coupling reaction of 2-0-benzyl-3,4-di-0-p-methoxybenzoyl-a-L-fucosyl bromide (115) and catechol 114 the fucosylation of 114 with 115 proceeded in the complete position-selective and a-stereoselective manner, providing exclusively a-fucoside 116 (Scheme 20), and the a-stereoselectivity of the reaction was ascribed to the internal 1,4-remote participation of the p-methox-ybenzoyl group (Fig. 9) [72],... 

SCHEME 8.10 Total synthesis of pseudopterosin (G-J) aglycon by Sherburn et al. [30]. 

Scheme 9.51, which shows the cyclization by the LBA in a single step to the tricyclic product in 75% yield with 87% ee [21b]. This process is clearly initiated by protonation of the internal olefinic jt-bond to form a bicyclic acetylene, which then undergoes a second (and slower) cyclization to generate the close core analog of pseudopterosin tricycle. The successful employment of this scenario is based on the lower proton affinity of C=C triple bond relative to C=C double bond. 

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