Acid-labile Protective Groups Research Articles

Photocatalytic Cleavage of Trityl Protected Thiols and Alcohols

AbstractWe report the visible light photocatalytic cleavage of trityl thioethers or ethers under pH-neutral conditions. The method results in the formation of the respective symmetrical disulfides and alcohols in moderate to excellent yield. The protocol only requires the addition of a suitable photocatalyst and light rendering it orthogonal to several functionalities, including acid labile protective groups. The same conditions can be used to directly convert trityl-protected thiols into unsymmetrical disulfides or selenosulfides, and to cleave trityl resins in solid phase organic synthesis.

A Ring Contraction of 2,3-Di- O-Silylated Thiopyranosides To Give Thiofuranosides under Mildly Acidic Conditions.

A pyranose ring contraction of ethyl 1-thio-β-d-galactopyranosides has been discovered that proceeds with retention of aglyconunder mildly acidic conditions (aq TFA in CH2Cl2). Key factors for success of this rearrangement are the presence of bulky silyl (TIPS or TBDPS) substituents at both O-2 and O-3 and a free hydroxy group at C-4 (derivatives with acid-labile protective groups at O-4 will also engage in this reaction). The rearrangement cleanly proceeds for 2,3-di- O-TIPS derivatives with two hydroxy groups at C-4 and C-6, acid-labile TES groups at O-4 and O-6, or one acyl substituent (Bz, ClAc) at O-6. A possibility to switch the direction of the debenzylidenation reaction in 4,6- O-benzylidene-2,3-di- O-TIPS/TBDPS derivatives by the choice of an acid (TFA, which cleanly gives furanose, versus AcOH, which cleaves benzylidene acetal only) may present an advantage in the divergent synthesis of selectively protected glycosyl donors (either in furanose or pyranose form) useful for the synthesis of biologically important oligosaccharides.

Triindolyl Macrocycle as a Molecular Platform in the Synthesis of Sumanene-Containing Polyphenols

A new strategy has been suggested for the synthesis of sumanene-containing polyphenols chemically bound to a molecular platform based on the triindolyl macrocycle. The initial assembly has been obtained by the Suzuki–Miyaura reaction of a bromo-containing indolyl macrocycle and boryl derivative of N,N'-disumanenylaniline. Subsequent benzylation with 3,5-dimethoxybenzyl bromide, exhaustive demethylation of the modified macrocycle, and partial blocking of the corresponding phenolic hydroxyls by two different acid-labile protective groups have led to the formation of the target polyphenol containing sumanene fragments. The obtained polyphenol has allowed us to develop on its basis a new positive resist for electronbeam nanolithography. This resist can realize topological structures with resolution of 9–12 nm.

Tetraindole Derivatives of Porphyrins as Building Blocks in the Synthesis of Monodisperse Polyphenols

A new strategy for the synthesis of monodisperse polyphenols chemically bound to a rigid thermally stable molecular platform has been suggested. The platform has been prepared by the Suzuki–Miyaura reaction of a tetraboryl porphyrin derivative and 3-(4′-bromophenyl)-4,6-dimethoxyindole. Subsequent reactions of complete demethylation of obtained tetraindole and partial blocking of the corresponding phenolic hydroxyls by acid-labile protective groups have led to the formation of a final modified polyphenol compound of the porphyrin series. On the basis of the this polyphenol, a positive photoresist for lithography with exposure radiation at a wavelength of 13.5 nm has been developed; the photoresist affords the fabrication of topological structures with 16-nm resolution.

Fast and Facile Synthesis of 4-Nitrophenyl 2-Azidoethylcarbamate Derivatives from N-Fmoc-Protected α-Amino Acids as Activated Building Blocks for Urea Moiety-Containing Compound Library.

A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino acids, including those having functionalized side chains with acid-labile protective groups, were directly transformed into 4-nitrophenyl 2-azidoethylcarbamate derivatives in 1 h via a one-pot two-step reaction. These urea building blocks were utilized for the preparation of a series of urea moiety-containing mitoxantrone-amino acid conjugates in 75-92% yields and parallel solution-phase synthesis of a urea compound library consisted of 30 members in 38-70% total yields.

Development of a new microwave-assisted cleavable backbone amide linker (BAL): a comparative study

A thorough comparative study to demonstrate the properties of a new microwave labile backbone amide linker is presented. A cyclic pentapeptide, cyclo(Trp-Gln-Gly-beta-Ala-Phe), was used as a model and synthesized following 16 different conditions. The new backbone amide linker is stable towards acid and base at r.t., and can be cleaved at elevated temperature in trifluoroacetic acid under microwave irradiation, avoiding the use of aggressive reagents like HF. The new linker is compatible with Boc- as well as Fmoc-strategy and allows the cleavage of acid labile side chain protective groups at r.t., prior to cleavage of the cyclic pentapeptide from the resin.

Phosphomolybdic Acid Supported on Silica Gel: An Efficient, Mild and Reusable Catalyst for the Chemoselective Hydrolysis of Acetonides

Carbohydrate acetonides were chemoselectively cleaved to the corresponding diols by using environmentally benign phosphomolybdic acid (H3PMo12O40) supported on silica gel (PMA-SiO2) at ambient temperature in a short span of 5-7 minutes in acetonitrile. Acid-labile protective groups such as THP, TBS, TBDPS, MOM, OMe and PMB were found to be stable under the reaction conditions.

Glycosyl Phosphatidylinositol (GPI) Anchor Synthesis Based on Versatile Building Blocks – Total Synthesis of a GPI Anchor of Yeast

For the design of a synthesis of target molecule 1 the retrosynthetic analysis yielded building blocks 2–5, of which ceramide 2-phosphite derivative 2 and aminoethyl phosphite derivative 5 are known. The generation of α-glucosaminyl (16)inositol building block 3 was based on pseudodisaccharide 6 which was selectively benzoylated at 6b-O and then selectively benzylated at 3b-O to give 3. The synthesis of tetramannosyl building block 4 started from known ortho ester derivative 8 which was transformed into versatile mannosyl donors 13 and 18 and into acceptor 22. Reaction of 13 with 22 gave α-disaccharide 23, deacetylation and then mannosylation with 18 gave trisaccharide 25; ensuing deacetylation and mannosylation with 13 gave tetrasaccharide 27; deallylation, acetylation, regioselective removal of the anomeric O-acetyl group and treatment with CCl3CN/DBU afforded 4. Glycosylation of 3 with donor 4 led to pseudohexasaccharide 31 in high yield. Replacement of the O-acyl groups by O-benzyl groups and then exchange of the menthyloxycarbonyl group by an O-acetyl group gave 36 which enabled regioselective attachment of 2 and 5. To this end, the 6e-O-silyl group was removed and then the aminoethyl phosphate residue was attached with reagent 5 to give 38 in high yield. 1a-O-Deacetylation and then reaction with 2 afforded 40 as fully protected 1 which was liberated in two steps; treatment with acid removed all acid labile protective groups and finally catalytic hydrogenation afforded the desired GPI anchor 1 which could be fully structurally assigned.

Use of acid-labile protective groups for carbohydrate moieties in synthesis of glycopeptides related to type II collagen

β-D-Galactopyranosyl and α-D-glucopyranosyl-β-D-galactopyranosyl moieties carrying silyl, isopropylidene and 4-methoxybenzyl protective groups have been attached to the amino acid 5-hydroxy-L-norvaline. The resulting glycosylated building blocks were used in Fmoc solid-phase synthesis of glycopeptides related to a fragment from type II collagen which is immunodominant in a mouse model for rheumatoid arthritis. The protective groups used for the carbohydrate moieties were completely removed during acid catalyzed cleavage of the glycopeptides from the solid phase under conditions which left the O-glycosidic bonds intact.

Use of Acid-labile Protective Groups for Carbohydrate Moieties in Synthesis of Glycopeptides Related to Type II Collagen

Use of Acid-labile Protective Groups for Carbohydrate Moieties in Synthesis of Glycopeptides Related to Type II Collagen

Evaluation of Alicyclic Methacrylate Resist with a .GAMMA.-Butyrolactone Protective Group for 193-nm Lithography.

We proposed the use of 3-hydroxy-γ-butyrolactone and 2-methyl-2-adamantanol as acid-labile protective groups in a methacrylate polymer for building a 193-nm resist with good lithographic and cost performance. In this paper, we investigated the influence of the quantity of 2, 2′- azobisisobutyronitrile (AIBN) used in the polymer synthesis, the effect of the polymer molecular weight (Mw) on the lithographic performance, and heat-flow resistance of the resist. We discuss the impact of the AIBN loadings, on the pattern profiles as well as the sensitivity and suitable molecular weight for high resolution. Through the investigation, we found that the quantity of AIBN had little influence on the pattern profiles and the lower loading afforded higher sensitivity. We also found that the suitable Mw was around 15, 000. The resist displayed no pattern deformation up to 130°C, which is higher than that for a Novolak resist.

Solid-Phase Synthesis of Glycopeptides: Immunological Studies with T Cell Stimulating Glycopeptides

Stepwise solid-phase synthesis using glycosylated amino acids as puilding blocks has been shown to be the most general and efficient approach for preparation of glycopeptides. The a-amino group of the glycosylated amino acids should be protected with the fluoren-9-ylmethoxy­ carbonyl (Fmoc) group whereas acetyl groups, or acid labile protective groups, are suitable for the carbohydrate hydroxyl groups. Due to the recent rapid development of Fmoc solid-phase glycopeptide synthesis glycopeptides are increasingly being made available for investigations in biological sciences, such as studies of the cellular immune response to glycopeptides. These studies have established that glycopeptides are bound well by both class I and . II MHC molecules and elicit a carbohydrate specific T cell response after immunization, provided that the position for the glycan is chosen carefully in the centre of the peptide. Such a location most likely allows contacts between carbohydrate and the CDR3s of the T cell receptor. Investigations using viral glycoproteins suggest that the large N-linked glycans influence the T cell response to glycoproteins, but that this does not involve specific interactions between the glycan and the T cell. Furthermore, viruses seem to exploit mutations which introduce or delete N-linked glycans to escape from attack by T cells. In contrast, studies have revealed that the smaller 0-linked carbohydrates found on collagen or mucins are able to elicit a carbohydrate specific T cell response. Altogether, these immunological studies have suggested novel applications in medicine, including generation of a cellular immune response to carbohydrate antigens found on pathogens or tumour cells, and induction of tolerance in autoimmune rheumatoid arthritis.

New Protective Groups in Alicyclic Methacrylate Polymers for 193-nm Resists.

We used a methacrylate polymer with two acid labile protective groups, mevalonic lactone and 2-methyl-2-adamantanol (Fig. 1), for a 193-nm resist.[1-4] THF resist demonstrated high sensitivity and a high resolution as a single layer resist. In this paper, we investigated polar five protective groups in place of THF lactone group to obtain necessary properties for good lithographic performance. We discuss THF impact of THF polarity and acid cleavability of THF protective groups to make a good match to 2-methyl-2-adamantyl group. Among THF selected protective groups, we found that 3-hydroxy-γ-butyrolactone yielded acceptable lithographic performance.

Preparation of a glycopeptide analogue of type II collagen — Use of acid labile protective groups for carbohydrate moieties in solid phase synthesis of O-linked glycopeptides

A glycopeptide analogue of the immunodominant T cell epitope on type II collagen has been prepared by solid phase synthesis. Preparation of a glycosylated amino acid from two monosaccharide units that carried silyl and isopropylidene protective groups and Fmoc 5-hydroxynorvaline was essential for the synthesis. After assembly of the glycopeptide the carbohydrate protective groups were removed simultaneously with acid catalyzed cleavage from the solid phase.

Mild conditions for the removal of acid-labile protective groups

Hydrogen peroxide-trichloroacetic acid is an effective reagent combination for the mild cleavage of acid-labile protective groups.