Rational synthesis of meso-substituted chlorin building blocks

Chlorins provide the basis for plant photosynthesis, but synthetic model systems have generally employed porphyrins as surrogates due to the unavailability of suitable chlorin building blocks. We have adapted a route pioneered by Battersby to gain access to chlorins that bear two meso substituents, a geminal dimethyl group to lock in the chlorin hydrogenation level, and no flanking meso and beta substituents. The synthesis involves convergent joining of an Eastern half and a Western half. A 3,3-dimethyl-2,3-dihydrodipyrrin (Western half) was synthesized in four steps from pyrrole-2-carboxaldehyde. A bromodipyrromethane carbinol (Eastern half) was prepared by sequential acylation and bromination of a 5-substituted dipyrromethane followed by reduction. Chlorin formation is achieved by a two-flask process of acid-catalyzed condensation followed by metal-mediated oxidative cyclization. The latter reaction has heretofore been performed with copper templates. Investigation of conditions for this multistep process led to copper-free conditions (zinc acetate, AgIO(3), and piperidine in toluene at 80 degrees C for 2 h). The zinc chlorin was obtained in yields of approximately 10% and could be easily demetalated to give the corresponding free base chlorin. The synthetic process is compatible with a range of meso substituents (p-tolyl, mesityl, pentafluorophenyl, 4-[2-(trimethylsilyl)ethynyl]phenyl, 4-iodophenyl). Altogether four free base and four zinc chlorins have been prepared. The chlorins exhibit typical absorption spectra, fluorescence spectra, and fluorescence quantum yields. The ease of synthetic access, presence of appropriate substituents, and characteristic spectral features make these types of chlorins well suited for incorporation in synthetic model systems.     

Synthesis of conjugates based on chlorin and isosteviol building blocks

Conjugates containing ent-beyerane carbocyclic frameworks on the periphery of a porphyrin macrocycle were prepared by acylation of chlorin e₆ derivatives with hydroxyl and amino groups using ent-16-ketobeyeran19-oic acid chloride (diterpenoid isosteviol). Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 165-169, March-April, 2009.     

Solid-phase synthesis of new S-glycoamino acid building blocks

Efficient synthesis of unprotected S-glycoamino acid building blocks in the solid phase by coupling a sugar 1-thiolate with iodine activated fluoren-9-ylmethoxycarbonyl (Fmoc) protected amino acids.     

Convenient synthesis and isolation of trifluoromethylthio-substituted building blocks

Various aryl-, heteroaryl-, and alkyl mercaptanes (RSH, 1a–r) were treated with a slight excess of NaH suspended in DMF to make the appropriate sodium thiolates (RSNa), which then reacted with 1.3 equivalent of CF₃I at room temperature for overnight to afford the appropriate trifluoromethyl sulfides (CF₃SR, 2) in fair to good yields. The radical chain alkylation reaction was effective without the use of UV irradiation with all but three substrates (thiosalicylic acid, 1k; 2-mercaptobenzimidazole, 1q; and 3-mercaptopropionic acid, 1r).Steam-distillation was found as an effective and easy to upscale means for the isolation of these volatile and water immiscible sulfides. The CF₃I reagent gas was conveniently weighed and delivered to the reaction mixture by the balloon technique or as a preliminary made stock solution in DMF or DMSO. The sulfides 2 obtained here were assayed by GC and characterized by ¹H, ¹³C, ¹⁹F NMR and MS spectroscopy.     

Asymmetric synthesis of alkaloids using polyfunctionalized chiral building blocks

Enantiopure N‐sulfinyl‐δ‐amino‐β‐ketoesters and isoquinolones, prepared from sulfinimines (N‐sulfinyl imines) are a new class of polyfunctionalized chiral building blocks. These building blocks provide easy access to enantiomerically pure, functionalized piperidines and tetrahydroisoquinolines with a minimum of chemical manipulation and protecting‐group chemistry. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:486–492, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10090     

Convenient multi-gram scale synthesis of polybrominated imidazoles building blocks

The multi-gram scale polybromination of variously substituted imidazoles has been realized using a stoichiometric amount of the Br₂-DMF complex. Good yields have been obtained compared to other methods using large amounts of acetic acid-sodium acetate buffer.     

De novo synthesis of L-colitose and L-rhodinose building blocks

A divergent, practical, and efficient de novo synthesis of fully functionalized L-colitose (3,6-dideoxy-L-galactose), 2-epi-colitose (3,6-dideoxy-L-talose), and L-rhodinose (2,3,6-trideoxy-L-galactose) building blocks has been achieved using inexpensive, commercially available (S)-ethyl lactate as the starting material. The routes center around a diastereoselective Cram-chelated allylation that provides a common homoallylic alcohol intermediate. Oxidation of this common intermediate finally resulted in the synthesis of the three monosaccharide building blocks.     

Efficient synthesis of phosphotyrosine building blocks using imidazolium trifluoroacetate

We have successfully employed imidazolium trifluoroacetate as a replacement for tetrazole for efficient synthesis of phosphotyrosine. This modification is compatible with the protecting groups commonly used in solution phase and Fmoc-solid phase peptide synthesis.     

Divergent synthesis and optoelectronic properties of oligodiacetylene building blocks

A new and divergent synthetic route to oligodiacetylene (ODA) building blocks has been developed via Sonogashira reactions under a reductive atmosphere. These central building blocks provide a new way for rapid preparation of long ODAs. In addition, we report on their optoelectronic properties which are dependent on their end cap. Finally, the formation of their radical cations, and their optical properties and reactivity towards nucleophiles are investigated.     

Glycosyl thioimidates as versatile building blocks for organic synthesis

This review discusses the synthesis and application of glycosyl thioimidates in chemical glycosylation and oligosaccharide assembly. Although glycosyl thioimidates include a broad range of compounds, the discussion herein centers on S-benzothiazolyl (SBaz), S-benzoxazolyl (SBox), S-thiazolinyl (STaz), and S-benzimidazolyl (SBiz) glycosides. These heterocyclic moieties have recently emerged as excellent anomeric leaving groups that express unique characteristics for highly diastereoselective glycosylation and help to provide a streamlined access to oligosaccharides.     

Solid-phase polyamine synthesis using piperazine and piperidine building blocks

[reaction: see text]. Polyamines containing piperidine and piperazine moieties have been synthesized on solid support using SN2 alkylation of resin-bound secondary amines with 2-nitrobenzenesulfonates (nosylates). The effect of solvent on this alkylation was investigated. The methodology was employed for the total synthesis of novel analogues of wasp polyamine toxins (philanthotoxins).     

Epoxy ketones as versatile building blocks in organic synthesis

The major advances made in the functionalisation of racemic and optically active epoxy ketones where one or several stereogenic centres are either preserved or modified are reviewed. Some relevant applications to the synthesis of natural products and biologically active compounds are also described.     

Caged phospho-amino acid building blocks for solid-phase peptide synthesis

Three 1-(2-nitrophenyl)ethyl-caged phospho-amino acids have been synthesized for use in standard N(alpha)-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (SPPS). The most common naturally occurring phospho-amino acids, serine, threonine, and tyrosine, were prepared as protected caged building blocks by modification with a unique phosphitylating reagent. In previous work, caged phospho-peptides were made using an interassembly approach (Rothman, D. M.; Vazquez, M. E.; Vogel, E. M.; Imperiali, B. Org. Lett. 2002, 4, 2865-2868). However, this technique is limited to creating peptides without oxidation sensitive residues C-terminal to the amino acid to be modified and the methodology involves synthetic manipulations on the solid phase that may limit the utilization of the methodology. Herein we report the facile synthesis of N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-serine 1, N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-threonine 2, and N-alpha-Fmoc-phospho(1-nitrophenylethyl-2-cyanoethyl)-L-tyrosine 3. These building blocks allow the synthesis of any caged phospho-peptide sequence using standard Fmoc-based SPPS procedures.     

Enantioselective synthesis of alpha-methyl-D-cysteine and lanthionine building blocks via alpha-methyl-D-serine-beta-lactone

[reaction: see text] We report here the enantioselective synthesis of Boc-alpha-methyl-d-cysteine(PMB)-OH and lanthionine building blocks through the regioselective ring opening of key intermediate Boc-alpha-methyl-d-serine-beta-lactone.     

Design and synthesis of macromolecular structures from self-assembling building blocks

The self-assembling properties of a variety of building-blocks are used to generate different types of nanostructures, e.g. molecular golfballs, molecular tubes, and molecular braids.     

Synthesis of 5-aminothiazoles as building blocks for library synthesis

A convenient route to 4-phenyl-5-aminothiazoles is described, which offers control over substitution at the 2-position. 2-N-Acylglycinamides were dithionated and a subsequent TFAA-mediated cyclisation step was followed by removal of the 5-N-trifluoroacetyl group providing the free amines. Though applicable generally the method was found to be most effective when introducing aromatic substituents at the 2-position, whereupon moderate overall yields of the 5-amino compounds were obtained.     

Synthesis of enantiomeric-pure cyclohexenyl nucleoside building blocks for oligonucleotide synthesis

Lipases were used for the resolution of (±) (4aR, 7R, 8aS)-2-phenyl-4a,7,8,8a-tetrahydro-4H-1,3-benzodioxine. This separation was carried out on preparative scale and used for the synthesis of eight phosphoramidites of cyclohexenyl nucleosides (d- and l-series).     

Design and synthesis of unnatural heparosan and chondroitin building blocks

Triazole linked heparosan and chondroitin disaccharide and tetrasaccharide building blocks were synthesized in a stereoselective manner by applying a very efficient copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction of appropriately substituted azido-glucuronic acid and propargyluted N-acetyl glucosamine and N-acetyl galactosamine derivative, respectively. The resulting suitably substituted tetrasaccharide analogues can be easily converted into azide and alkyne unit for further synthesis of higher oligosaccharide analogues.