THP Group Research Articles

The linear and nonlinear optical properties of organometallic chromophores derived from ferrocene, [Fe 2(η 5-C 5H 5) 2(CO) 2(μ-CO)(μ-CCH 3)] +[BF 4] − and terthienyl spacers. Crystal structure of 2-[( E)-2-ferrocenylethenyl]-5-(2-thienyl)thiophene

Several chromophores based on ferrocene, [Fe 2(η 5-C 5H 5) 2(CO) 2(μ-CO)(μ-CCH 3)] + and terthiophene or dithienylbenzo[ c]thiophene have been synthesized. Both thienyls have been shown to act as good donor end groups in their own right but contrary to our expectations the benzo[ c]thiophene merocyanine has a lower hyperpolarizablity (344×10 −30 esu) than its thienyl congener (650×10 −30 esu). The structure of 2-[( E)-2-ferrocenylethenyl]-5-(2-thienyl)thiophene has been determined by single crystal X-ray diffraction. The terminal thienyl (thp) group is disordered over two orientations about the bithienyl C(sp 2)C(sp 2) bond such that the two sulfur atoms in either thp ring are positioned trans/ cis in the ratio 0.628(4):0.372(4). The integrity of the alkenyl CC remains with a bond length of 1.332(2) Å and the CC lengths adjacent are 1.453(4)/1.441(4) Å. Twisting of the rings from planarity occurs along the Fc–CC–(thp)–(thp) axis: the angle which the ethenylthiophene CCC 4H 2S moiety makes with the C 5H 4 is 11.2(2)°, and with the major orientation of the disordered terminal thienyl group, 16(1)°.

Tetrabutylammonium tribromide (TBATB)-MeOH: An efficient chemoselective reagent for the cleavage of tert-butyldimethylsilyl (TBDMS) ethers

TBDMS, THP, and DMT ethers are efficiently deprotected with tetrabutylammonium tribromide in methanol. The apparent order of stability of different protecting group is phenolic TBDMS > 1 degrees OTBDPS > 2 degrees OTBDMS > 2 degrees OTHP > 1 degrees OTHP > 1 degrees OTBDMS > 1 degrees ODMT. TBDMS ether has been cleaved selectively in the presence of isopropylidine, Bn, Ac, Bz, THP, and TBDPS groups. This method is high yielding, fast, clean, safe, cost-effective, and therefore most suitable for practical organic synthesis.

New Synthesis of the Alkaloid Polonicumtoxin C

Two new short syntheses of the alkaloid polonicumtoxin C ( 3) are presented. In the first pathway, polonicumtoxin C was obtained in two steps by alkylation of 6-methyl-2,3,4,5-tetrahydropyridine with E-4-bromo-3-methyl-1-(tetrahydro-2-pyranyloxy)-2-butene 7 and subsequent deprotection of the THP group. In the second pathway, the cyclic ketimine was constructed via a short sequence of reactions involving (a) sequential alkylation of the N-(isopropylidene)isopropylamine with N, N-disilylprotected ω-bromopropylamine and E-4-bromo-3-methyl-1-(tetrahydro-2-pyranyloxy)-2-butene 7, (b) transimination and deprotection, the latter two reactions occurring in one step.

Synthesis of Farnesol Analogues through Cu(I)-Mediated Displacements of Allylic THP Ethers by Grignard Reagents.

The synthesis of a family of farnesol analogues, incorporating aromatic rings, has been achieved in high yields through the development of a regioselective coupling of allylic tetrahydropyranyl ethers with organometallic reagents. The allylic THP group is displaced readily by Grignard reagents in the presence of Cu(I) halides but is stable in the absence of added copper. Thus, an allylic THP group can fulfill its traditional role as a protecting group or serve as a leaving group depending on reaction conditions. An improved synthesis of (2E,6E)-10,11-dihydrofarnesol also has been accomplished using this methodology, and some preliminary studies on the reactivity and regioselectivity of THP ether displacements were conducted. The farnesol analogues reported herein may be useful probes of the importance of nonbonding interactions in enzymatic recognition of the farnesyl chain and allow development of more potent competitive inhibitors of enzymes such as farnesyl protein transferase.

Copper(II) Chloride Dihydrate: A Catalytic Agent for the Deprotection of Tetrahydropyranyl Ethers (THP Ethers) and 1-Ethoxyethyl Ethers (EE Ethers)

Tetrahydropyranyl ethers (THP groups) and 1-ethoxyethyl ethers (EE groups) are removed upon refluxing in 95% EtOH or Me2CO–H2O (95:5) in the presence of a catalytic amount of copper(II) chloride dihydrate (2–5 mol%).

Copper(II) Chloride Dihydrate: A Catalytic Agent for the Deprotection of Tetrahydropyranyl Ethers (THP Ethers) and 1-Ethoxyethyl Ethers (EE Ethers)

Tetrahydropyranyl ethers (THP groups) and 1-ethoxyethyl ethers (EE groups) are removed upon refluxing in 95% EtOH or Me2CO–H2O (95:5) in the presence of a catalytic amount of copper(II) chloride dihydrate (2–5 mol%).

Preparation of ω-tetrahydropyran-2-ylsulfanylalkylmagnesium chlorides: Useful reagents for the synthesis of 1-(ω-mercaptoalkyl)-1,2-dihydrobuckminsterfullerenes (C 60)

ω-Tetrahydropyran-2-ylsulfanylalkylmagnesium chlorides are prepared as Grignard reagents containing protected mercaptoalkyl chains, which are useful for the direct introduction of ω-mercaptoalkyl chains to electrophiles. In order to prove the usefulness of these reagents, they were reacted with buckminsterfullerene (C 60) to give 1-(ω-mercaptoalkyl)-1,2-dihydrobuck minsterfullerenes after the deprotection of THP group with TFA.

Synthesis and Characterization of Zwitterionic Block Copolymers

Zwitterionic poly(2-(dimethylamino)ethyl methacrylate-block-methacrylic acid) (PDMAEMA-block-PMAA) copolymers are synthesized by group transfer polymerization using 2-tetrahydropyranyl methacrylate (THPMA) as a protected monomer for the acid block. Subsequent thermolysis led to quantitative removal of the tetrahydropyranyl groups, but control experiments indicated significant broadening of the molecular weight distribution (MWD) of a PDMAEMA homopolymer under the same conditions. Hence this deprotection route was considered unsatisfactory. Acid hydrolysis of the block copolymers under mild conditions also led to quantitative removal of the THP groups, as judged by 1H NMR spectroscopy. This deprotection chemistry was adopted as our preferred route, since it did not lead to MWD broadening of the same PDMAEMA homopolymer. A series of zwitterionic blocks were synthesized with good control over both molecular weight and copolymer composition. The aqueous solubility vs. pH behavior of these copolymers was determined by acid titration. Finally, the reversible micellization of these copolymers in aqueous media was examined using dynamic light scattering and variable temperature 1H NMR spectroscopy.

Metallated α-alkoxypropargyl and γ-alkoxyallenyl derivatives: Applications in some aldol reactions towards diterpene synthesis

The allenyl titanium 11a, prepared using Yamamoto's conditions reacted with different aldehydes 12a-c to produce the anti acetylenic diols 13a-c. In a synthetic approach to erigerol 1 this reaction was applied to the aldehyde 4 and thr expected key intermediate 13d was obtained in 40% yield after removal of the THP group. During this study the α-alkoxypropargylstannane 14 and the α-alkoxyallenylstannane 15 were prepared in good yields after transmetallation of the corresponding lithio derivatives 5b and 7b by Ti(O i Pr) 4 or Et 2ZnCl.

Oligosaccharide Analogues of Polysaccharides. Part 6. Orthogonal protecting/activating groups in an improved binomial synthesis of ‘acetyleno‐oligosaccharides’

AbstractBromination of the monosilylated dialkynylated monomer 1a (Scheme 1), dimer 3 and tetramer 5 by N‐bromosuccinimide (NBS) in the presence of CF3COOAg gave 2, 4, and 6, respectively, in over 93%. Similar conditions led to bromodesilylation. Either silyl group of the diprotected monomer 1c was selectively removed by bromolysis. On the one hand, bromodesilylation of 1c gave 2 in yields varying between 80 and 99%. On the other hand, bromodesilylation of 7, obtained from 1c by hydrolytic removal of the tetrahydro‐2H‐pyran‐2‐yl (Thp) group, yielded 91% of 8. Mechanistic considerations suggested that the deprotective bromination should be improved by replacing the Me3Si by a Me3Ge group. Indeed, bromodegermylation of 1b was quantitative and ca. 60 times faster than bromodesilylation of 1c. The Me3Si and Me3Ge groups can be used for an orthogonal protection/activation of dialkynes. This was shown by desilylating 12 to 11 (Scheme 2), while bromination yielded 13. Both reactions proceeded in high yields; 9 was isolated as a minor by‐product of 13. The reactivity towards bromolysis decreases in the series H‐DOPS > Me3Ge ≈ H > Me3Si > Thp‐DOPS (DOPS = [dimethyl(oxy)‐p ropyl]dimethylsilyl). Orthogonal bromolysis of DOPS‐ and Me3Ge‐substituted dialkynes is slightly more selective than the one of Me3Si‐ and Me3Ge‐substituted analogues. Coupling of 7 with the bromoalkyne 2 gave the dimer 15 (76%), 14 (2%), and 16 (4%) (Scheme 3). The binomial synthesis was optimized so that each cycle, doubling the size of the precursor, requires the minimal number of transformations (Scheme 4). The orthogonally protected monomer 1b, dimer 19, and tetramer 22 were, on the one hand, hydrolyzed to the alcohols 18 (95%), 21 (91%), and 24(91%), respectively, and, on the other hand, bromodegermylated to 2 (99%), 4 (97%), and 6(93%). Cross‐coupling of 18 with 2, 21 with 4, and 24 with 6 gave the orthogonally protected dimer 19 (73%), tetramer 22 (87%), and octamer 25 (83%), respectively.

Synthesis of 9-(2-Deoxy-2-Fukuoro-β-D- Abinoruranosyl)Hypoxhine. The First Direct Introduction of A 2′-β-Fldoro Substituent in Ppepormed Purine Nucleosides. Studies Directed Toward the Synthesis of 2′-DEOXY-2′-Substituted Arabppmocebosides. 8.1

Abstract The 3′, 5′-di-O-acetyl-, 3′-, 5′-di-O-balzyl-, 3′-O-acety -5-O-trityl- and 3′-, 5′ -di-O-trityl-2′-O-triflyl-1-benzylhnosine (8c, 15, 20C, and 27, respectively) were prepared and subjected to nucleophilic reaction with TASF. Thus, 3′, 5′-O-(1, 1, 3, 3-tetraisopropyldisiloxanyl)-1-benzylinosine (5c) was triflylated, desilylated, and then acetylated to give 8c. Also, 5c was converted into the 2′-O-tetrahydropyrnyl (W) derivative 11 which was desilylated and then benzylated to give 2′-O-tetrahydropyranyl-O3′, O5′, N1-tribenzylinosine (13). Removal of the THP group from 13 followed by triflylation afforded 2′-O-triflyld-O3′,O5′ N1-tribenzylinosine (15). 3′-O-Acetyl-2′ -O-triflyl-,O5′,N1-inosine (20) was prepared frmn 5′ -O-trityl-1-benzylhh (18c) by conversion into the 2′-, 3′-O-(di-n-butylstannylene) derivative which was treated with triflyl chloride and then acetylated. Treatment of 1-benzyl-inosine (4c) with trityl chloride in pyridine containing p-dimethylamino-pyridine afforded a mixture of 2′-,...

The Utility of 2′-Thp Group in the Synthesis of the Relatively Long RNA Fragments on the Solid Phase

Abstract The stability of 2′-O-tetrahydropyranyl (Thp) group during several acidic treatments used for removal of 5′-O-9-(4-methoxy)phenyl xanthenyl (Mox) group in synthesis of 30 nucleotide long uridine molecules on the solid supports via cyanoethylphosphoramidite method is discussed.

Synthesis of 1‐ethyl‐1‐(2‐hydroxyethyl)aziridinium‐1,2‐14C2 chloride (1) ([14C]AF64A)

Abstract1‐Ethyl‐1‐(2‐hydroxyethyl)aziridinium‐1,2‐14C2 chloride (1) ([(14C]AF64A), the labelled analogue of a selective presynaptic cholinotoxin, was prepared from labelled ethylene oxide. The synthetic intermediate, 1,2‐14C2‐2[ethyl[2‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]ethyl]amino]ethanol, obtained in good yield by the reaction of 2‐[(tetrahydro‐2H‐pyran‐2‐yl)oxy]diethylamine with [14C] ethylene oxide, was converted to the corresponding ethyl chloride derivative using CH3SO2Cl/n‐BuLi. Subsequent removal of the THP group under mild acidic condition gave the mono‐armed mustard as a stable hydrochloride salt in an overall chemical yield of 46% and radiochemical yield of 27%. Conversion of the mustard compound to the corresponding aziridinium species was followed by 1H NMR.

Chemical synthesis of the 24 RNA fragments corresponding to hop stunt viroid.

A general and practical synthetic method of oligoribonucleotides (10-20 mers) by using the cyanoethyl phosphoramidite approach was described. In this experiment 9-phenylxanthen-9-yl (Pix) and 9-(4-methoxy)phenylxanthen-9-yl (Mox) groups were employed for the 5'-hydroxyls and tetrahydropyranyl (Thp) group was used for the 2'-hydroxyl protecting groups. In addition, suitable acyl groups were introduced for the protection of the lactam functions of guanine and uracil moieties.

The practical synthesis of RNA fragments in the solid phase approach

The combined use of the 2′-tetrahydropyran-4-yl(Thp group and 5′-9-phenylxanthen-9-yl(Pix) group or (4-methoxy)phenylxanthen-9-yl(Mox) group gave satisfactory results in the solid phasesynthesis of medium sized RNA fragments.

Chemical Synthesis of RNA Fragments Related to the C4N Hypothesis

Abstract Summary. Several oligoribonucleotide fragments which are related to the C4N hypothesis, were synthesized by both the liquid and solid phase methods via the phosphotriester approach, in which the combination of the 2′-Thp group with the 5′-DMTr group was used for chain elongation.

ChemInform Abstract: Synthesis of (2S,4aS,8aR)‐(‐)‐1,1,4a‐Trimethyl‐2‐decalol, an Inhibitor of Steroid Biosynthesis.

AbstractThe ketol (Ia) is protected by the THP group [‐ (Ib)] and alkylated to give (III) as a stereoisomeric mixture, which is methylated to afford a 71:29 mixture of stereoisomers (V).