hepta-1,6-diyne

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl acetylenedicarboxylate (1.0 ml, 6.3 mmol) and dicarbonylcyclopentadienylcobalt (0.1 ml, 0.62 mmol) were added dropwise to a solution of 1,6-heptadiyne (0.72 ml, 6.3 mmol) in xylene (5 ml), and stirred at 80° C. for 5 days. To the reaction solution was added dilute hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried and concentrated under reduced pressure, followed by purifying the residue by silica gel chromatography (chloroform, successively hexane:ethyl acetate=10:1) to give 0.36 g of diethyl 5,6-indandicarboxylate. extracted with ethyl acetate The organic layer was washed with saturated brine dried concentrated under reduced pressure by purifying the residue by silica gel chromatography (chloroform, successively hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,6-heptadiyne (1.242 ml, 10.85 mmol) and ethyl cyanoformate (1.063 ml, 10.85 mmol) in dry degassed 1,4-dioxane (100 ml) under argon at rt was treated with cyclopentadienyl-Cobalt(I)-dicarbonyl (0.293 g, 1.628 mmol) and then heated at reflux for 18 h. Reaction was then evaporated, treated with toluene (100 ml), re-evaporated, dissolved in DCM (100 ml), filtered through a short pad of Kieselguhr, eluting with DCM, organic extracts evaporated, chromatographed (0-100% DCM:40-60 Petroleum ether then 0-10% methanol/DCM) to give product as an impure brown oil (427 mg, 21%). degassed 1,4-dioxane (100 ml) under argon at rt heated at reflux for 18 h Reaction was then evaporated treated with toluene (100 ml) re-evaporated dissolved in DCM (100 ml) filtered through a short pad of Kieselguhr eluting with DCM, organic extracts evaporated chromatographed (0-100% DCM

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mg of product 1 are dissolved in 1.1 ml of distilled water; a solution of 140 μl of 1,6-Heptadiyne in 9.86 ml of DMSO are prepared separately, whereas 23.2 mg of doxorubicin hydrochloride are dissolved in 0.5 ml of distilled water. The solution of hyaluronic acid is mixed with that of doxorubicin and with 0.2 ml of that of 1,6-Heptadiyne; 0.1 ml of an aqueous solution obtained with 50 mg of CuSO4.5H2O in 1 ml of H2O and 0.1 ml of an aqueous solution of 20 mg of ascorbic acid are then added. The mixture is stirred vortically for a few minutes. The rapidly formed gel (see FIG. 28) incorporates the doxorubicin hydrochloride inside.