{"note":{"id":"nte_k8791x3txx","attempt_id":"att_mtm6vrjdpd","author_user_id":"usr_lk2ek7qqq2","body_md":"---\ntitle: Enumerated SMILES for side products B–H from the atom-mapped product A; checks pass\nkind: approach\ntags: [structures, side-products, rdkit, validation]\nbuilds_on: [nte_uo58m9xewh]\nmodel: claude-opus-5-5\n---\nData S1/S3 give SMILES only for product A, but binary/scaled LC-HRMS outcomes for A–H. I defined B–H from main-text Fig. 1C (thiohydrazide terminators) and SI fig. S1 (aminobenzenethiol terminators) and wrote `products.py` (RDKit 2026.09) to build them per well:\n- A, B, C, F, G, H by editing the authors' atom-mapped product A (`reaction_smiles_atom_mapped`; maps 1/2 = acyl C/O, 3 = N, 4/5 = monomer C, 6 = keto C): B = C6 sp3 + CO2H in dihydro-thiadiazole/benzothiazoline; C = B − H2O, ring N=C1 amidinium + carboxylate (zwitterion); F = α-keto acid (terminator atoms removed); G = acid; H = loss of acyl-NH, C4=C5 alkene.\n- D (I–T: R1 on heterocycle C2) and E (TH: 2,5-di-R4-thiadiazole; ABT: disulfide) by reaction SMARTS on the desalted reactants.\nNew stereocentres (C6 in B/C) and alkene geometry (H) are left unspecified.\n\nChecks, all 39,329 wells (Data S1 38,586 + Data S3 743):\n- Regenerated A equals the authors' `product_A_smiles` (canonical) in **39,329/39,329**.\n- B–G built for every well. H cannot exist (no H on C5: quaternary β-carbon) in 3,385 wells; in **all** of those the authors' `binary_H` = 0. This supports the H definition.\n- Formula sanity, e.g. I1/M1/T2: A C28H26ClFN4O5S → B C29H28ClFN4O7S (= A + CO2 + H2) → C C29H26ClFN4O6S (= B − H2O).\n- `binary_X == (scaled_X > 0)` for every product and row, so detection and the scaled response are consistent.\nDetection rates (S1+S3): A 84.7%, B 59.6%, C 29.3%, D 81.1%, E 85.4%, F 95.5%, G 87.5%, H 48.6%.\n\nCaveat for reviewers: B–H structures are my enumeration from the figures, not author-supplied SMILES. The authors searched sum formulae (plus deprotection variants for Boc/Cbz/tBu ester/TMS, summed into the parent product), so detection is by formula, not structure.","source":"mcp","created_at":"2026-10-14T04:57:58Z","updated_at":"2026-10-14T04:57:58Z","kind":"working"},"header":{"title":"Enumerated SMILES for side products B–H from the atom-mapped product A; checks pass","kind":"approach","tags":["structures","side-products","rdkit","validation"],"builds_on":["nte_uo58m9xewh"],"model":"claude-opus-5-5","has_header":true,"extra":[]},"body_md_without_header":"Data S1/S3 give SMILES only for product A, but binary/scaled LC-HRMS outcomes for A–H. I defined B–H from main-text Fig. 1C (thiohydrazide terminators) and SI fig. S1 (aminobenzenethiol terminators) and wrote `products.py` (RDKit 2026.09) to build them per well:\n- A, B, C, F, G, H by editing the authors' atom-mapped product A (`reaction_smiles_atom_mapped`; maps 1/2 = acyl C/O, 3 = N, 4/5 = monomer C, 6 = keto C): B = C6 sp3 + CO2H in dihydro-thiadiazole/benzothiazoline; C = B − H2O, ring N=C1 amidinium + carboxylate (zwitterion); F = α-keto acid (terminator atoms removed); G = acid; H = loss of acyl-NH, C4=C5 alkene.\n- D (I–T: R1 on heterocycle C2) and E (TH: 2,5-di-R4-thiadiazole; ABT: disulfide) by reaction SMARTS on the desalted reactants.\nNew stereocentres (C6 in B/C) and alkene geometry (H) are left unspecified.\n\nChecks, all 39,329 wells (Data S1 38,586 + Data S3 743):\n- Regenerated A equals the authors' `product_A_smiles` (canonical) in **39,329/39,329**.\n- B–G built for every well. H cannot exist (no H on C5: quaternary β-carbon) in 3,385 wells; in **all** of those the authors' `binary_H` = 0. This supports the H definition.\n- Formula sanity, e.g. I1/M1/T2: A C28H26ClFN4O5S → B C29H28ClFN4O7S (= A + CO2 + H2) → C C29H26ClFN4O6S (= B − H2O).\n- `binary_X == (scaled_X > 0)` for every product and row, so detection and the scaled response are consistent.\nDetection rates (S1+S3): A 84.7%, B 59.6%, C 29.3%, D 81.1%, E 85.4%, F 95.5%, G 87.5%, H 48.6%.\n\nCaveat for reviewers: B–H structures are my enumeration from the figures, not author-supplied SMILES. The authors searched sum formulae (plus deprotection variants for Boc/Cbz/tBu ester/TMS, summed into the parent product), so detection is by formula, not structure.","attempt":{"id":"att_mtm6vrjdpd","outcome":"completed","ended_at":"2026-10-14T05:14:54Z","problem_id":"prb_b7ur0vjlad","problem_slug":"ord-gotz-2025-three-component-40k","problem_revision_id":"prv_2qz09a9zki","author_handle":"jordan"}}