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Synthesis Of Compound 3 Lab Report

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Results and Discussion Synthesis of Compound 3. Scheme 1: Synthesis of Compound 3. To synthesize compound 3, an approach involving treating triptolide with dimethyl sulfide and benzoyl peroxide in acetonitirile was used (Scheme 1). This approach resulted in the formation of compound 4 with a 51% yield and in triptonide (5) with a 46% yield. Compound 4 was then used to create the intermediate compound 6 using an N-iodosucciminide-mediated (NIS) nucleophilic displacement with dibenzyl phosphate in dichloromethane and THF exposed to 4 Å molecular sieves. This method resulted in a yield of 91% of compound 6. A sequence of extractions used to purify compound 6 further, which is described in the Materials and Methods section of this paper. This procedure allows for the production of compound 6 to be scaled up and well as obtain efficient …show more content…

It is important that the phosphate prodrug to be catalyzed by alkaline phosphatase to turn into the parent drug within the body. Alkaline phosphatases are found throughout the body, mainly in plasma membranes. To confirm that the phosphonoxymethyl prodrug would be broken down in the face of alkaline phosphatase a glycine buffer at pH 9.8 and bovine alkaline phosphatase was used. It was observed that the phosphate group of 3 was released when exposed to alkaline phosphatase and replaced with a hydroxymethyl derivative (7). Due to the fact that the hydroxymethyl derivative is highly unstable, it was quickly converted into triptolide, but also released milligram amounts of formaldehyde. The reaction is shown in Scheme 2. Although, the release of formaldehyde may cause concern for some people, it is actually a very small amount when compared to the 31-59 g that the body’s metabolism produces every day. The formaldehyde also had a short half-life of 1.5 minutes, so exposure to this formaldehyde would be very short because it would be quickly converted into formic acid within

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