364 W.C.Dumlap et al.I Methods 42(2007)358-376 receptors [8].Of these candidates,the cyclic peptide apli- dime()om the grancd} Brvostatin (34)from the bryozoan Bugula neritina pro gressed to Phase II trials before being discontinued.Ectein ascidin 743(ET submitted for registration in the EU on for treatment of sarcoma.Discodermolide(36)from the imical sudillhatuributd to be products of resident commensal microorganisms [52] 2receptors [8]. Of these candidates, the cyclic peptide apli￾dine (33) from the ascidian Aplidium albicans has been granted Orphan Drug status in Europe for the treatment of acute lymphocytic leukemia [53] and is in Phase II trials. Bryostatin 1 (34) from the bryozoan Bugula neritina pro￾gressed to Phase II trials before being discontinued. Ectein￾ascidin 743 (ET 743) (35) from the tunicate Ecteinascidia turbinata is in Phase III trials with PharmaMar and was submitted for registration in the EU on 1 August, 2006 for treatment of sarcoma. Discodermolide (36) from the sponge Discodermia spp. advanced to Phase I examination before being discontinued by Novartis due to excessive drug toxicity, although some analogues are advancing in pre￾clinical studies. All of these natural agents are attributed to be products of resident commensal microorganisms [52]. O HN O N O HO HO OH spongouridine (28) O HN O N O HO HO OH spongothymidine (29) N N NH2 N N O HO OH HO Ara-A (Vidarabine®) (30) HN N N N O OH O H2N acyclovir (Zovirax®) (31) HN N O O CH3 HO O N3 azidothymidine (AZT) (32) NH OH O O O O HN O N O N Me OMe O O O N H O Me N O N O O aplidine (33) O O O O HO O MeOOC COOMe O O H OH OH OAc OH H bryostatin 1 (34) N N O HO O O H H H H H H O NH HO O S O H H OH AcO ecteinascidin 743 (ET 743) (35) O O OH OH OH O OH NH2 O discodermolide (36) 364 W.C. Dunlap et al. / Methods 42 (2007) 358–376