Our next objective was to establish a concise and chemoenzymatic approach to the synthesis of cyctryptomycin A and B (1-2) that possess neuroprotective activity with potential efficacy against neurodegenerative diseases such as ALS, Alzheimer's, and Parkinson's diseases. Our strategy involved with the mild and scalable Zr-catalyzed dimerization reaction to synthesize tetratryptomycin A (3) on a decagram scale. Notably, the synthetic route initiated a simple and cost-effective reaction (Scheme 1B). Specifically, 6 was synthesized by protecting the nitrogen atom on the indole and the primary amine with a Boc group, utilizing the natural form of L-tryptophan ethyl ester. Subsequently, 7 was synthesized as a single diastereomer by bromocyclization of 6 using NBS. The slow addition of NBS during bromocyclization of 6 was crucial for obtaining the single compound 7, as a rapid addition resulted in inseparable diastereomeric mixtures. Compound 7 was then dimerized to 8 using a Cp2ZrCl2 catalyzed reaction on a decagram scale, driven by the formation of a strong and stable Zr-Br bond. Notably, the addition of dppe (10 mol%) was essential for the Cp2ZrCl2 catalyzed dimerization reaction, as it helped trap trace amounts of residual metal in the reagent and prevented reproducibility issues on both 1 g and 10 g scales, with yields decreasing to 25% without dppe. The resulting dimerized product 8 was simultaneously deprotected with TMSI to remove the four Boc groups, and the resulting Boc-protected L-tryptophan was condensed with HATU to yield 10. Flash vacuum pyrolysis (FVP) was then employed to rapidly construct two diketopiperazines simultaneously in a single step, yielding a total of 21 g of tetratryptomycin A (3). The macrocyclization of tetratryptomycin A (3) by coupling the C22-C18' and N-C18' positions was a significant step towards a scalable synthesis of cyctryptomycin A and B (1-2).