Two-Directional Synthesis of Polycyclopropanes. An Approach to the Quinquecyclopropane Fragment of U-106305

McDonald, W. Scott; Verbicky, Christopher A.; Zercher, Charles K.

doi:10.1021/jo961136b

Cited by 42 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cyclopropanation with diethyl zinc/diiodomethane in either THF or Et 2 O consistently failed to consume all of the alkene which complicated purification as the starting material and the cyclopropanated product have identical R f values on TLC. When dichloromethane was employed, however, ester 10 was produced in 86−92% yield with no evidence of 9b . Saponification of ester 10 in KOH/EtOH followed by subsequent acidification afforded the cyclopropyl acid 11 in 92% yield.…”

Section: Introductionmentioning

confidence: 99%

Six- vs Seven-Membered Ring Formation from the 1-Bicyclo[4.1.0]heptanylmethyl Radical: Synthetic and ab Initio Studies

et al. 1998

View full text Add to dashboard Cite

The viability of utilizing 1-bicyclo[4.1.0]heptanylmethyl radical (3) to serve as a progenitor of seven-membered carbocycles was examined. Rate constants for the rearrangement of this radical to 3-methylenecycloheptyl radical (4) and 2-methylenecyclohexyl-1-methyl radical (6) were measured using the competition method of 3 with thiophenol over the temperature range of −75 to 59 °C. Arrhenius functions were calculated for the conversions of 3 to 4 and 3 to 6 and found to be log(k/s-1) = (12.38 ± 0.20) − (5.63 ± 0.23)/θ and log(k/s-1) = (11.54 ± 0.32) − (5.26 ± 0.37)/θ, respectively. The rate constants for these conversions at 25 °C are 1.86 × 108 s-1 and 5.11 × 107 s-1, respectively. Hence, the seven-membered ring-expanded carbocycle is formed 3.6 times faster at 25 °C than the nonexpanded species. This suggests that the 1-bicyclo[4.1.0]heptanylmethyl radical system may be synthetically useful in seven-membered ring-forming methodology. Preliminary theoretical examination of this radical system qualitatively predicted the experimentally determined energies of activation: PMP4/6-31G*//HF/6-31G* ΔE a (3 → 6 − 3 → 4) = 3.0 kcal/mol with zero point energy correction. The HF/6-31G* optimized reaction coordinate stationary points suggest cyclopropyl substituent eclipsing interactions play an important role in determining the kinetic outcome of these rearrangements.

show abstract

Section: Introductionmentioning

confidence: 99%

Six- vs Seven-Membered Ring Formation from the 1-Bicyclo[4.1.0]heptanylmethyl Radical: Synthetic and ab Initio Studies

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The intermediate alcohols 6 − 9 were obtained by monotritylation of commercially available diols 3 − 5 , with the exception of 8 , the corresponding diol of which is not commercially available. This ( E )-buten-2-yl derivative 8 was prepared by reduction of the butynyl alcohol 7 with LiAlH 4 . Condensation of the alcohols 6 − 9 with N 3 -BzT in the presence of PS-triphenylphosphine and DIAD in dry THF, followed by debenzoylation by treatment with 1 M NaOH in a dioxane/H 2 O (1:1) solution, afforded the target compounds 10 − 13 in good yields (61−89%).…”

Section: Chemistrymentioning

confidence: 99%

Acyclic Nucleoside Analogues as Novel Inhibitors of Human Mitochondrial Thymidine Kinase

et al. 2002

View full text Add to dashboard Cite

A series of acyclic nucleoside analogues of 5'-O-tritylthymidine have been synthesized and evaluated as potential human mitochondrial thymidine kinase (TK-2) inhibitors. In this series, the sugar moiety of the parent 5'-O-tritylthymidine has been replaced by aliphatic chains including (E)- and (Z)-butenol, butynol, or butanol. Among them the (Z)-butenyl derivative (10) showed an IC(50) against TK-2 of 1.5 microM, being 1 order of magnitude more potent than the parent 5'-O-tritylthymidine. This lead compound has been further modified by replacing the thymine base by other pyrimidine bases such as 5-iodouracil, 5-ethyluracil, 5-methylcytosine, 3-N-methylthymine, or 5,6-dihydrothymine, as well as by the purine base guanine. The trityl group has also been replaced by different aliphatic and aromatic acyl moieties including tert-butylacetyl, hexanoyl, decanoyl, and diphenylacetyl moieties. The evaluation of the compounds against TK-2 and the phylogenetically close HSV-1 TK has shown that the base moiety plays a crucial role in their interaction against these pyrimidine nucleoside kinases. Also, the presence of a lipophilic substituent, preferentially an aromatic moiety such as diphenylmethyl or triphenylmethyl, is required for efficient TK-2 inhibition. Whereas some compounds showed marked specificity for either TK-2 (i.e, the 5,6-dihydrothymine derivative, 26) or HSV-1 TK (i.e., the butynyl derivative, 11), some others, including the (Z)-and (E)-butenyl derivatives 10 and 12, showed significant inhibition against both enzymes. They also proved to be inhibitory against HSV-1 TK in intact human osteosarcoma cells that were transduced with the HSV-1 TK gene.

show abstract

“…It is well-known that this process can also be carried out in an enantioselective fashion. 14 The hydroxy group of 24 was then replaced by iodide. 15 Treatment of iodide 25 with triphenylphosphine in refluxing toluene gave phosphonium salt 26.…”

Section: Synthesis Of Vinyl Triflate 12mentioning

confidence: 99%

Studies towards the total synthesis of solanoeclepin A: synthesis and potato cyst nematode hatching activity of analogues containing the tetracyclic left-hand substructureElectronic supplementary information (ESI) available: further experimental details. See http://www.rsc.org/suppdata/p1/b2/b202020n/

Benningshof

IJsselstijn

Wallner

et al. 2002

J. Chem. Soc., Perkin Trans. 1

View full text Add to dashboard Cite

Two-Directional Synthesis of Polycyclopropanes. An Approach to the Quinquecyclopropane Fragment of U-106305

Cited by 42 publications

References 31 publications

Six- vs Seven-Membered Ring Formation from the 1-Bicyclo[4.1.0]heptanylmethyl Radical: Synthetic and ab Initio Studies

Six- vs Seven-Membered Ring Formation from the 1-Bicyclo[4.1.0]heptanylmethyl Radical: Synthetic and ab Initio Studies

Acyclic Nucleoside Analogues as Novel Inhibitors of Human Mitochondrial Thymidine Kinase

Contact Info

Product

Resources

About