The product standard aza(dethia)CoA ( ) was a challenge to generate using our workflow due to side reactions or limited turnover during chemoenzymatic preparation. If the ATP regeneration system was used with aza(dethia)pantetheine (18), a large amount of 2 was generated due to acetylation by acetyl phosphate as an expected side product. If an excess of ATP is used rather than the ATP regeneration system 6 can be generated in small quantities but the major product is 3'-dephosphoaza(dethia)CoA, which appears to be a very poor substrate for E. coli CoaE. Therefore, we turned to alternative routes for 6, Scheme 2 with details in the supplemental information. Starting with N-Boc-ethylenediamine and pantothenic acid acetonide, we produced intermediate 19 using mixed anhydride coupling. We generated the azide intermediate 20 using previously published methods. Selective acetonide deprotection of 19 to N-Boc-aza(dethia)pantetheine ( ) and 20 to azide(dethia)pantetheine (22) was achieved with careful application of formic acid. The N-protected pantetheines were converted to CoAs chemoenzymatically yielding 23 and 24. The final deprotection of 23 to 6 using TFA was possible with careful monitoring. The conversion of 24 to 6 was examined with a few reducing reagents with TCEP being superior to the reagents triphenylphosphine, tributylphosphine, tris(hydroxymethyl)phosphine, or borohydride. We confirmed the identity of 6 through comparison of products by HPLC, HRMS and NMR, Supplemental Figure . Our synthesis of the malonyl-CoA analogs 3/4 via Meldrum's acid used fewer steps than previous methods and gave high yields before purification as judged by analytical LCMS. Furthermore, our strategy of using Meldrum's acid is applicable to 2-substituted analogs for use with various polyketide synthase and intermediary metabolic enzymes. All of the analogs 1-6 are completely stable overnight in buffer at pH 6, 7 and 8 used for the subsequent enzymology experiments.