This review deals with developments of new types of protecting groups for suger hydroxyl groups in nucleic acid chemistry. The details of introduction of an orthoester type of acid-lablie protecting group, 1, 3-benzodithiol-2-yl (BDT), into primary and secondary alcohols are described. This group is applied to synthesis of DNA and RNA fragments and also used as precusor of the methyl group for the synthesis of 5-carboxymethyl aminomethy 1-2'-O-methyluridine recently discovered from E. Coli tRNA. Two kinds of 4, 4', 4 ''-trisubstituted trityls, tris (benzoyloxy) trityl (TBTr) and tris (levulinyloxy) trityl (TLTr), are described in detail as base-labile and hydrazine-labile protecting groups, respectively, for primary alcohols. The 4, 4', 4'' -tris (4, 5-dichlorophthalimido) trityl (CPTr) group derived from a dye, pararosaniline, is introduced as useful 5'-hydroxyl protecting group which can be easily removed by one step treatment with hydrazine. A successful application of this group to the synthesis of a branched RNA is also shown. Finally, the versatile utility of a new functionalized trityl, 3- (imidazol-1-ylmethyl) -4', 4''-dimethoxytrityl (IDTr), which serves as not only 5'-hydroxyl protecting group but also catalytic site for condensation, is reviewed.
Homochiral acetals derived from chiral diol and carbonyl compound are recognized as “Chiralsynthon” of the carbonyl group, whose chirality enables to introduce a new asymmetric center into the molecule. The reaction is based on the selective coordination of the organometallic reagent or Lewis acid to one of the two acetal oxygen. Using thus obtained homochiral acetals this article surveys the recent development of asymmetric syntheses involving the selective cleavage of the acetal or induction of the asymmetry to neighboring functional group.
Lipophilic cyclic peptides from marine invertebrates constitute a growing class of naturally occurring antineoplastic and/or cytotoxic substances. These peptides commonly contain two kinds of unusual amino acids, thiazole and oxazoline amino acids, as their constituents. Our continuing efforts on peptide synthesis using two organophosphorus coupling reagents, diphenyl phosphorazidate (DPPA, (C6H5O) 2P (O) N3) and diethyl phosphorocyanidate (DEPC, (C2H5O) 2P (O) CN), have achieved the syntheses of dolastatin 3 (the proposed structure), ascidiacyclamide, patellamides A, B, and C, ulithiacyclamide, and ulicyclamide. Cytotoxic activity of all of synthesized cyclic peptides and their derivatives was investigated using L1210 murine leukemia cells in culture. Ulithiacyclamide having the oxazoline and disulfide functions showed marked cytotoxicity, ID50=0.04 μg/ml.
Polyketides, biosynthetic intermediates of natural aromatic compounds, are useful in organic synthesis. Various polyketides were prepared by using the Claisen- type reaction of polyanions of β- ketoesters, and the intramolecular condensation to give aromatic compounds were examined. Based on the studies, a new synthetic method for the polycyclic aromatic compounds was developed. The process allows the synthesis of polyoxygenated naphthalene, anthracene, naphthacene, and pentacene derivatives.
Sesbanimide A and B, potent antitumor alkaloides, isolated from the seeds of the leguminous plant, Sesbania drummondii, constitute unusually attractive targets for total synthesis because of their remarkable antitumor activity and novel structures. This review deals with three independent total syntheses of these novel alkaloids which include our first total synthesis of natural sesbanimide A and B. Concerning formation of the AB-ring system in an optically active form, introduction of the C5-unit into the AB-ring system, and construction of the C-ring system, the synthetic strategies and tactics so far reported are discussed.