The cover picture shows the synthesis of formylporphyrins by Umpolung reactions that use 1,3‐dithian‐2‐ylporphyrins as masked synthons. This method offers a new pathway for the preparation of free‐base and metallo formylporphyrins under mild conditions. Grignard and Wittig reactions have been performed to demonstrate the wide range of applications for formylporphyrins. Details are discussed in the article by M. O. Senge et al. on p. 3833 ff.

Brush border lactase-phlorizin hydrolase carries two catalytic sites. In the human enzyme lactase comprises Glu-1749, phlorizin hydrolase Glu-1273. The proteolytic processing of pro-lactase-phlorizin hydrolase by (rat) enterocytes stops two amino acid residues short of the N-terminus of`mature' final, brush border lactase-phlorizin hydrolase. Only these two amino acid residues are removed by luminal pancreatic protease(s), probably trypsin.z 1998 Federation of European Biochemical Societies.

Dedicated to Prof. Albert Eschenmoser on the occasion of his 75th birthday With the aim to develop a general approach to a total synthesis of aminoacylated t-RNAs and analogues, we describe the synthesis of stabilized, aminoacylated RNA fragments, which, upon ligation, could lead to aminoacylated t-RNA structures. Novel RNA phosphoramidites with fluoride-labile 2'-O-[(triisopropylsilyl)-oxy]methyl ( tom) sugar-protecting and N-{{2-[(triisopropylsilyl)oxy]benzyl}oxy}carbonyl ( tboc) baseprotecting groups were prepared (Schemes 4 and 5), as well as a solid support containing an immobilized N 6 -tboc-protected adenosine with an orthogonal (photolabile) 2'-O-[(S)-1-(2-nitrophenyl)ethoxy]methyl ( (S)-npeom) group (Scheme 6). From these building blocks, a hexameric oligoribonucleotide was prepared by automated synthesis under standard conditions (Scheme 7). After the detachment from the solid support, the resulting fully protected sequence 34 was aminoacylated with l-phenylalanine derivatives carrying photolabile N-protecting groups (3 42 and 43; Scheme 9). Upon removal of the fluoride-labile sugar-and nucleobaseprotecting groups, the still stabilized, partially with the photolabile group protected precursors 44 and 45, respectively, of an aminoacylated RNA sequence were obtained (Scheme 9 and Fig. 3). Photolysis of 45 under mild conditions resulted in the efficient formation of the 3'(2')-O-aminoacylated RNA sequence 46 (Fig. 4).Additionally, we carried out model investigations concerning the stability of ester bonds of aminoacylated ribonucleotide derivatives under acidic conditions (Table) and established conditions for the purification and handling of 3'(2')-O-aminoacylated RNA sequences and their stabilized precursors.

A new synthetic method for the N-alkyloxycarbonylation of adenine and guanine nucleosides was developed and used for the preparation of RNA-phosphoramidites carrying photolabile sugar and nucleobase protecting groups. From these building blocks, a heptameric oligoribonucleotide was prepared by automated synthesis, followed by detachment from the solid support and photolytic deprotection under mild conditions. The presented strategy allows a simple preparation of 3'-O-aminoacylated RNA-sequences.A severe limitation in the chemical synthesis of oligonucleotide analogues is the requirement to remove the commonly used acyl-type nucleobase protecting groups with strong nucleophiles such as NH 3 or MeNH 2 . For instance, some of the naturally occurring modified nucleosides, e.g. pseudouridine and dihydrouridine are not stable under the conditions required for deprotection of the standard base protecting groups benzoyl (for cytidine and adenosine) and isobutyryl (for guanosine). In this context, more labile base protecting groups such as phenoxyacetyl have been developed and extend the range of tolerated modifications significantly. 1 Another approach involves protection groups such as allyloxycarbonyl which are removed under nonnucleophilic conditions by the assistance of Pd 0 -complexes. 2One of the mildest deprotection is offered by photolytic removal of appropriate protecting groups. We had earlier developed an efficient method for the synthesis of RNA phosphoramidites carrying the photolabile 2'-O-[(2-nitrobenzyl)oxy]methyl sugar protecting group, which can be removed under mild, weakly acidic conditions. 3 In the above mentioned context, we now wanted to extend the scope of RNA-synthesis by preparing phosphoramidite building blocks with photocleavable sugar and base protecting groups.Specifically, we were interested in a general, nonenzymatic synthesis of 3'-O-aminoacylated t-RNA analogues which allow the biosynthetic, ribosome-mediated incorporation of unnatural amino acids into proteins. 4,5 So far, such aminoacylated t-RNA analogues were synthesized by enzymatic ligation of truncated t-RNAs with 3'-O-aminoacylated dimers. The latter compounds were prepared by condensation of a weekly activated, N-protected amino acid with a non-or partially protected ribodinucleotide. 4,5,6,7 A severe limitation is the sensitivity of the ester-linkage towards basic hydrolysis at pH-values, where the enzymatic ligation step is carried out (t 1/2 (pH 7.5) = 22 min.). 5Our retrosynthetic scheme for the preparation of 3'-Oaminoacylated t-RNA analogues differs from the known concept by excluding all enzymatic steps. We are planning to attach aminoacylated RNA-fragments to the 3'-end of truncated, chemically synthesized t-RNAs by chemical ligation. 8 The non-enzymatic ligation needs a template which is provided by the 5'-region of the truncated t-RNA; its 3'-end serves thereby as primer. This disconnection requires the synthesis of an aminoacylated riboheptanucleotide which is able to form at least three base-pairs during ligation.He...

Self-complementary oligodeoxynucleotides containing 3,6-disubstituted phenanthrenes adopt highly stable, hairpin-like structures. The thermodynamic stability of the hairpin mimics depends on the overall length of the phenanthrene building block. Hairpin loops composed of a phenanthrene-3,6-dicarboxamide and ethylene linkers were found to be optimal. The hairpin mimics are more stable than the analogous hairpins containing either a dT 4 or dA 4 tetraloop. Model studies indicate that the thermodynamic stability of the hairpin mimics is primarily due to aromatic stacking of the phenanthrene-3,6-dicarboxamide onto the adjoining base pair of the DNA duplex.