Described are multi-ring antioxidant products comprising at least one sulfur-bridged aromatic hydrocarbon compound substituted on at least one of its aromatic rings by at least one sterically hindered 3,5-dihydrocarbyl-4-hydroxybenzyl moiety. Such products have the formula:
R—S.sub.n—R[—S—R].sub.m
wherein each R is, independently, an aromatic hydrocarbon group having 6-12 carbon atoms, wherein m is 0-20, wherein n is 1-6 when m is 0, and when n is 1, m is 1-20; and wherein at least one of R, R.sup.1, and R.sup.2 is substituted by at least one such sterically hindered moiety. The preparation of such products and their use as antioxidants in compositions normally susceptible to oxidative degradation in oxygen or air, e.g., liquid fuel and lubricants, are also described.

The present invention relates to a process for producing ajoene from allicin via a polymeric substrate, comprising the steps of heating allicin or an allicin solution at a predetermined temperature range such that at least a portion of the allicin is converted to ajoene to form an ajoene solution; and separating the ajoene from the ajoene solution; wherein at least one of the heating or separating steps is conducted via a polymeric substrate. The process for producing ajoene from allicin via a polymeric substrate further comprises a step of retaining the allicin or the allicin solution on the polymeric substrate before the heating step is conducted within or out of the polymeric substrate. The present invention also relates to ajoene or a composition comprising ajoene obtained by the process thereof.

The present invention relates to a process for producing ajoene from allicin via a polymeric substrate, comprising the steps of heating allicin or an allicin solution at a predetermined temperature range such that at least a portion of the allicin is converted to ajoene to form an ajoene solution; and separating the ajoene from the ajoene solution; wherein at least one of the heating or separating steps is conducted via a polymeric substrate. The process for producing ajoene from allicin via a polymeric substrate further comprises a step of retaining the allicin or the allicin solution on the polymeric substrate before the heating step is conducted within or out of the polymeric substrate. The present invention also relates to ajoene or a composition comprising ajoene obtained by the process thereof.

The present invention relates to a process for producing ajoene from allicin via a polymeric substrate, comprising the steps of heating allicin or an allicin solution at a predetermined temperature range such that at least a portion of the allicin is converted to ajoene to form an ajoene solution; and separating the ajoene from the ajoene solution; wherein at least one of the heating or separating steps is conducted via a polymeric substrate. The process for producing ajoene from allicin via a polymeric substrate further comprises a step of retaining the allicin or the allicin solution on the polymeric substrate before the heating step is conducted within or out of the polymeric substrate. The present invention also relates to ajoene or a composition comprising ajoene obtained by the process thereof.

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

A process of making N,N′-diacetyl-L-Cystine disodium salt, the process comprising: (i) Mixing hydroxy alkane (between 0.5-100 L, preferably between 0.5-10 L, more preferably between 1-3 L, most preferably 1 L per mol of cystine) with a sodium base (4.0 molar equivalents per mole of cystine) to form a cold solution at a temperature of from 5 to 10° C.; (ii) Adding cystine (1 molar equivalent) to said cold solution and stirring, for a sufficient time, to form a basic cystine solution; (iii) Optionally, Cooling the cystine solution to 5° C.; (iv) Adding acetyl chloride (2 molar equivalents per mole of cystine) portionwise, while maintaining the temperature between 3 and 50° C., preferably between 5 and 35° C., more preferably below 10° C., most preferably 5° C., thereby resulting in a white suspension; (v) Stirring said white suspension and allowing said suspension to warm up to a room temperature of 15° C. to 50° C., preferably 20° C. to 35° C., more preferably 20° C., thereby resulting in N,N′-diacetyl-L-Cystine disodium salt product dissolved in solution and sodium chloride by-product precipitated solid in said suspension. The present description discloses an exemplary process on a small laboratory scale (500 mg cystine educt; 688 mg product; 90% yield) (page 16; example 1).

A process of making N,N′-diacetyl-L-Cystine disodium salt, the process comprising: (i) Mixing hydroxy alkane (between 0.5-100 L, preferably between 0.5-10 L, more preferably between 1-3 L, most preferably 1 L per mol of cystine) with a sodium base (4.0 molar equivalents per mole of cystine) to form a cold solution at a temperature of from 5 to 10° C.; (ii) Adding cystine (1 molar equivalent) to said cold solution and stirring, for a sufficient time, to form a basic cystine solution; (iii) Optionally, Cooling the cystine solution to 5° C.; (iv) Adding acetyl chloride (2 molar equivalents per mole of cystine) portionwise, while maintaining the temperature between 3 and 50° C., preferably between 5 and 35° C., more preferably below 10° C., most preferably 5° C., thereby resulting in a white suspension; (v) Stirring said white suspension and allowing said suspension to warm up to a room temperature of 15° C. to 50° C., preferably 20° C. to 35° C., more preferably 20° C., thereby resulting in N,N′-diacetyl-L-Cystine disodium salt product dissolved in solution and sodium chloride by-product precipitated solid in said suspension. The present description discloses an exemplary process on a small laboratory scale (500 mg cystine educt; 688 mg product; 90% yield) (page 16; example 1).

A process of making N,N′-diacetyl-L-Cystine disodium salt, the process comprising: (i) Mixing hydroxy alkane (between 0.5-100 L, preferably between 0.5-10 L, more preferably between 1-3 L, most preferably 1 L per mol of cystine) with a sodium base (4.0 molar equivalents per mole of cystine) to form a cold solution at a temperature of from 5 to 10° C.; (ii) Adding cystine (1 molar equivalent) to said cold solution and stirring, for a sufficient time, to form a basic cystine solution; (iii) Optionally, Cooling the cystine solution to 5° C.; (iv) Adding acetyl chloride (2 molar equivalents per mole of cystine) portionwise, while maintaining the temperature between 3 and 50° C., preferably between 5 and 35° C., more preferably below 10° C., most preferably 5° C., thereby resulting in a white suspension; (v) Stirring said white suspension and allowing said suspension to warm up to a room temperature of 15° C. to 50° C., preferably 20° C. to 35° C., more preferably 20° C., thereby resulting in N,N′-diacetyl-L-Cystine disodium salt product dissolved in solution and sodium chloride by-product precipitated solid in said suspension. The present description discloses an exemplary process on a small laboratory scale (500 mg cystine educt; 688 mg product; 90% yield) (page 16; example 1).

The present invention includes methods for making and isolating N-acetylcysteine amide, (2R,2R′)-3,3′-disulfanediyl bis(2-acetamidopropanamide, diNACA), intermediates and derivatives thereof comprising: contacting cystine with an alcohol and a chlorinating reagent to form an organic solution containing L-cystine dimethylester dihydrochloride; combining dried or undried L-cystine dimethylester dihydrochloride with a triethylamine, an acetic anhydride, and an acetonitrile to form a di-N-acetylcystine dimethylester; mixing dried di-N-acetylcystine dimethylester with ammonium hydroxide to form a di-N-acetylcystine amide (diNACA); and separating dried di-N-acetylcystine dimethylester into N-acetylcysteine amide with dithiothreitol, triethylamine and an alcohol.