C-Nucleosides and related compounds. XV. The synthesis of D,L-2′-epi-showdomycin and D,L-showdomycin

Abstract

GEORGE JUST, T. J. LIAK. MU-ILL LIM, PIERRE POTVIN, and YOULA S. TSANTRIZOS. Can. J . Chem. 58,2024Chem. 58, (1980. The conversion of the Diels-Alder adduct of methyl P-nitroacrylate wlth furan to the title compounds and to D,L-2.5-anhydroglucose derivatives 1s described.GEORGE JUST, T. J. LIAK, MU-ILL LIM. PIERRE POTVIN et YOULA S. TSANTRIZOS. Can. J. Chem. 58,2024Chem. 58, (1980. On dkcrit la transformation du produit de la rkaction Dlels-Alder du mCthyle P-nitroacrylate avec le furane en dkrivis du DL-23-anhydroglucose, en D,L-2'-Ppi-showdomycine, et en showdomycine.As part of a programme to synthesize C-5a, accompanied by varying amounts of 6a. From nucleosides, we were interested in developing a the relative ratios of 5a to 6a as a function of reacmethod to prepare an arabinose derivative 8, bear-tion time, it was obvious that 5a was transformed to ing at the anomeric center a functionalized carbon 6a. Compound 5a was characterized as its acetate atom, which could serve as a precursor for the 5b. At this point, it became apparent that the synthesis of compounds such as ara-showdomycin tetrahydropyranyl protecting group obscured the (9b).nmr spectrum of 5a and 5b enough to make some of Reaction of furan with methyl P-nitroacrylate the assignments doubtful. The reaction sequence gave the known adducts l a and l b (1). Prolonged was therefore repeated with the dimethyl-terttreatment with m-chloroperbenzoic acid gave butylsilyl ether lactone 4e, providing 5e and 6b; 5e epoxides 2a and 2b, which upon treatment with was characterized as its pivalate Sf. Since Just and diazabicyclo[5.4.0]undec-Sene (DBU) gave ole-Ouellet (3) subsequently established in the analofinic epoxide 3. As expected (2a), nmr analysis of gous carbocyclic series that the pivalate group inthis compound revealed that the stereochemistry teracted with the hydroxy group generated in the of the epoxide function was exo, since the coupling subsequent ozonolysis-reduction sequence 5 + 7, constant between the bridgehead protons and the it was decided to block the hydroxy group in 5e as endo-protons cr to the epoxide was 0 Hz (dihedral its dimethyl-tert-butylsilyl ether 5g (4). Silylation angle -90" (2b)). of 5e proceeded in an unpredictable manner, proTreatment of endo-carbomethoxy epoxide 2b viding the disilylation product 5g, except for one with acetic acid and hydrochloric acid at 95°C for instance, in low yield. 2 h gave lactone 4a in 60% yield. There is ample Ozonolysis of the olefin 5g, followed by treatprecedent that lactonizations of this type proceed ment with dimethyl sulfide and the reduction of the in the manner depicted, and it has been recently resulting keto aldehyde, obtained in part as its hyreconfirmed in an unambiguous manner for a drate, with 4 equivalents of lithium tri-tert-butoxyclosely related system (12). aluminum hydride, gave diol ester 7d. Selective Attempts to acylate hydroxy lactone 4a with silylation of 7d gave the trisilyl ether 7f. That the acetic anhydride or pivaloyl chloride in pyridine silylation had proceeded wi...

Using ring-opening reactions of oxabicyclic compounds as a strategy in organic synthesis

“…Silyl protection gave alcohol 125 and reduction transformed the thioether linkage into the vicinal cis dimethyl groups found in (+)-nemorensic acid [137]. Previous synthetic studies that have employed ozonolysis as a means for cleaving oxabicyclic substrates include Meinwald's studies toward pederin [ 138], Just's synthesis of showdowmycin [139], Masamune's synthesis of avenaciolide [140], and Ohno's asymmetric syntheses of (+)-showdowmycin, (-)-cordycepin C, and (-)-6-azapseudouridine [ 141 a].…”

“Slim” Nucleosides and Nucleotides. I. Synthetic, Structural and Biophysical Investigations of Showdomycins

“…Also reported are our molecular modeling studies on homo-and heteropolymer duplexes containing sU-A or dsU-A pairs. Downloaded by [New York University] While there are several reported syntheses of showdomycin (18)(19)(20)(21)(22)(23)(24)(25)(26)(27), most of them are long, tedious, and low-yielding. Due to its brevity, we adopted the procedure of Barrett,et al (26) to prepare showdomycin, but with the following modifications (Scheme 1).…”

“…Ring closure of 14 was effected by sequential treatments with phenylselenyl chloride and 3% hydrogen peroxide to produceN-trityl-2'-deoxyshowdomycin (16) and its 1'-epimer (17) in a 60:40 ratio as determined by 1 H NMR Finally, deprotection of the maleimide nitrogen was carried out using TFNH 2 0 (50: 1 ). The two anomeric products, 2' -deoxyshowdomycin (~-anomer) ( 18) and 2' -deoxyepishowdomycin (a-anomer) (19), were separated by HPLC on a C 18 column using water as an eluent. Both anomers have the same melting point, but different NMR spectral data.…”

Specific Features of the Reaction of 2-Nitro- and 2-Bromo-2-Nitroethenylphosphonates with Furan

“…The interest to the Diels3Alder reaction with the participation of furan as a diene component arises from the possibility of obtaining oxabornenes which are widely used as intermediates for construction of the analogs of native C-nucleosides [3,4], hydrocarbons [5], and the other biologically active compounds [6].…”

“…We established that contrary to ethyl 3-nitroacrylate and its nitrile which react with furan in ether at 20oC for 1-2 days with the formation of adducts of diene condensation in the yields up to 92% [4,5], nitroethenylphosphonate I reacts with furan under more rigid conditions, that is at keeping a mixture of starting reagents, nitroethenylphosphonate and furan, in 1 : 2 ratio at 18320oC for 72 h. …”