@@ -1,4 +1,4 @@
-.PHONY: demo test lint ci clean bench-leakage bench-baseline bench-hidden-active generate phase3 pilot validate-scoring validate-scoring-strict external-predict pilot-confident presynth-qc gold-standard diversity
+.PHONY: demo test lint ci clean bench-leakage bench-baseline bench-hidden-active generate phase3 pilot validate-scoring validate-scoring-strict external-predict pilot-confident presynth-qc gold-standard diversity synthesis-order
 
 PYTHON := $(shell [ -f .venv/bin/python ] && echo .venv/bin/python || echo python3)
 PYTEST  := $(shell [ -f .venv/bin/pytest ] && echo .venv/bin/pytest || echo pytest)
@@ -118,5 +118,12 @@ diversity:
 		--panel-csv outputs/confident_panel.csv \
 		--out outputs/diversity_report.md
 
+synthesis-order:
+	PYTHONPATH=src $(PYTHON) -m openamp_foundry.cli synthesis-order \
+		--panel-csv outputs/confident_panel.csv \
+		--out-csv outputs/synthesis_order.csv \
+		--out-md outputs/synthesis_checklist.md \
+		--quantity-mg 5
+
 clean:
 	rm -rf outputs/*.jsonl outputs/*.md outputs/*.json outputs/evidence outputs/phase3_evidence .pytest_cache .ruff_cache
@@ -290,6 +290,36 @@ def build_parser() -> argparse.ArgumentParser:
         help="Output markdown report path.",
     )
 
+    synthesis_order = sub.add_parser(
+        "synthesis-order",
+        help=(
+            "Generate a vendor-ready synthesis order CSV and checklist from a panel CSV. "
+            "Runs pre-synthesis QC on every candidate and auto-fills N/C-term modifications, "
+            "purity spec, quantity, and special-handling notes."
+        ),
+    )
+    synthesis_order.add_argument(
+        "--panel-csv",
+        default="outputs/confident_panel.csv",
+        help="Panel CSV (candidate_id + sequence columns required).",
+    )
+    synthesis_order.add_argument(
+        "--out-csv",
+        default="outputs/synthesis_order.csv",
+        help="Output path for vendor-ready order CSV.",
+    )
+    synthesis_order.add_argument(
+        "--out-md",
+        default="outputs/synthesis_checklist.md",
+        help="Output path for synthesis checklist markdown.",
+    )
+    synthesis_order.add_argument(
+        "--quantity-mg",
+        type=float,
+        default=5.0,
+        help="Default order quantity in mg per peptide (default: 5.0). HIGH-difficulty peptides get 2×.",
+    )
+
     batch_pack = sub.add_parser(
         "batch-pack",
         help=(
@@ -366,6 +396,9 @@ def main(argv: list[str] | None = None) -> int:
     if args.command == "batch-pack":
         return _run_batch_pack(args)
 
+    if args.command == "synthesis-order":
+        return _run_synthesis_order(args)
+
     if args.command == "presynth-qc":
         return _run_presynth_qc(args)
 
@@ -631,6 +664,72 @@ def _run_generate_batch(args: argparse.Namespace) -> int:
     return 0
 
 
+def _run_synthesis_order(args: argparse.Namespace) -> int:
+    import csv as _csv
+    from datetime import datetime, timezone
+    from openamp_foundry.features.physchem import compute_features
+    from openamp_foundry.qc.order_generator import (
+        generate_synthesis_order,
+        write_order_csv,
+        write_synthesis_checklist,
+    )
+
+    panel_path = Path(args.panel_csv)
+    if not panel_path.exists():
+        print(json.dumps({"status": "error", "message": f"File not found: {args.panel_csv}"}))
+        return 1
+
+    panel = []
+    with open(panel_path, newline="", encoding="utf-8") as f:
+        for row in _csv.DictReader(f):
+            panel.append(row)
+
+    mu_h_map = {}
+    for row in panel:
+        seq = row["sequence"].strip().upper()
+        feats = compute_features(seq)
+        mu_h_map[row["candidate_id"]] = feats.get("hydrophobic_moment", 0.0)
+
+    qty = args.quantity_mg
+    order_rows, qc_results = generate_synthesis_order(
+        panel,
+        mu_h_map=mu_h_map,
+        default_quantity_mg=qty,
+        high_difficulty_quantity_mg=qty * 2,
+    )
+
+    generated_at = datetime.now(timezone.utc).isoformat()
+    write_order_csv(order_rows, args.out_csv)
+    write_synthesis_checklist(
+        order_rows,
+        qc_results,
+        args.out_md,
+        generated_at=generated_at,
+        panel_csv=args.panel_csv,
+    )
+
+    n_acetyl = sum(1 for r in order_rows if r["n_modification"] == "Ac-")
+    n_amide = sum(1 for r in order_rows if r["c_modification"] == "NH2")
+    n_high = sum(1 for r in order_rows if r["synthesis_difficulty"] == "HIGH")
+    total_mg = sum(float(r["quantity_mg"]) for r in order_rows)
+
+    print(json.dumps({
+        "status": "ok",
+        "n_candidates": len(order_rows),
+        "n_n_terminal_acetylation": n_acetyl,
+        "n_c_terminal_amide": n_amide,
+        "n_high_difficulty": n_high,
+        "total_quantity_mg": total_mg,
+        "out_csv": args.out_csv,
+        "out_md": args.out_md,
+        "disclaimer": (
+            "This order is computationally generated. Human expert review required "
+            "before submitting to vendor. No antimicrobial activity has been demonstrated."
+        ),
+    }, indent=2))
+    return 0
+
+
 def _run_presynth_qc(args: argparse.Namespace) -> int:
     import csv as _csv
     from datetime import datetime, timezone
 
@@ -0,0 +1,239 @@
+"""Vendor-ready synthesis order generator for AMP pilot panels.
+
+Reads a panel CSV, runs pre-synthesis QC on every candidate, and produces:
+  1. synthesis_order.csv  — GenScript-compatible order form (one row per peptide)
+  2. synthesis_checklist.md — human-readable per-candidate synthesis brief
+
+Columns in synthesis_order.csv:
+  pilot_rank, candidate_id, sequence, length, mol_weight_da,
+  n_modification, c_modification, purity_spec, quantity_mg,
+  synthesis_difficulty, special_handling
+"""
+from __future__ import annotations
+
+import csv
+from pathlib import Path
+from typing import TYPE_CHECKING
+
+if TYPE_CHECKING:
+    from openamp_foundry.qc.presynth_check import SynthQC
+
+
+# Canonical special-handling codes emitted for each QC flag category.
+# Kept short so they fit in a vendor order form cell.
+_HANDLING_MAP = {
+    "CYSTEINE": "N2 storage; check purity pre-assay",
+    "MET": "−80°C; check purity post-thaw",
+    "HYDROPHOBIC_RUN": "Solubility check 1 mM PBS",
+    "TRYPSIN_SITES": "Use serum-free media for initial MIC",
+    "DEAMIDATION_RISK": "pH 5-6 lyophilization buffer",
+    "ISOMERIZATION_RISK": "HPLC re-check post-reconstitution",
+    "TRP_PHOTOLABILITY": "Amber vials; red/dim light only",
+    "LOW_CHARGE": "Higher test concentrations may be needed",
+    "LONG_PEPTIDE": "Discuss yield with vendor; order extra crude",
+}
+
+
+def _extract_handling(flags: list[str]) -> str:
+    """Map QC flag strings to short handling notes, deduplicated."""
+    notes: list[str] = []
+    seen: set[str] = set()
+    for flag in flags:
+        for key, note in _HANDLING_MAP.items():
+            if flag.startswith(key) and note not in seen:
+                notes.append(note)
+                seen.add(note)
+    return "; ".join(notes)
+
+
+def generate_synthesis_order(
+    candidates: list[dict],
+    mu_h_map: dict[str, float] | None = None,
+    default_quantity_mg: float = 5.0,
+    high_difficulty_quantity_mg: float = 10.0,
+) -> tuple[list[dict], list["SynthQC"]]:
+    """Generate vendor-ready order rows and QC results for a candidate panel.
+
+    Args:
+        candidates: list of dicts with at minimum 'candidate_id' and 'sequence'.
+                    Optional keys: 'pilot_rank', 'ensemble', 'activity', 'safety'.
+        mu_h_map: {candidate_id: hydrophobic_moment} for hemolysis stratification.
+        default_quantity_mg: order quantity for LOW/MODERATE difficulty (default 5 mg).
+        high_difficulty_quantity_mg: order quantity for HIGH difficulty (default 10 mg).
+
+    Returns:
+        (order_rows, qc_results) — both aligned by index to the input candidates list.
+    """
+    from openamp_foundry.qc.presynth_check import check_panel
+
+    mu_h_map = mu_h_map or {}
+    qc_results = check_panel(candidates, mu_h_map=mu_h_map)
+
+    order_rows: list[dict] = []
+    for candidate, qc in zip(candidates, qc_results):
+        n_mod = "Ac-" if qc.n_acetylation_recommended else "Free"
+        c_mod = "NH2" if qc.c_amidation_recommended else "OH"
+
+        qty = (
+            high_difficulty_quantity_mg
+            if qc.synthesis_difficulty == "HIGH"
+            else default_quantity_mg
+        )
+
+        special = _extract_handling(qc.flags)
+
+        order_rows.append({
+            "pilot_rank": candidate.get("pilot_rank", ""),
+            "candidate_id": qc.candidate_id,
+            "sequence": qc.sequence,
+            "length": qc.length,
+            "mol_weight_da": qc.molecular_weight_da,
+            "n_modification": n_mod,
+            "c_modification": c_mod,
+            "purity_spec": ">95% HPLC",
+            "quantity_mg": qty,
+            "synthesis_difficulty": qc.synthesis_difficulty,
+            "special_handling": special,
+        })
+
+    return order_rows, qc_results
+
+
+def write_order_csv(order_rows: list[dict], out_path: str | Path) -> None:
+    """Write vendor-ready order CSV."""
+    out = Path(out_path)
+    out.parent.mkdir(parents=True, exist_ok=True)
+    fieldnames = [
+        "pilot_rank", "candidate_id", "sequence", "length", "mol_weight_da",
+        "n_modification", "c_modification", "purity_spec", "quantity_mg",
+        "synthesis_difficulty", "special_handling",
+    ]
+    with open(out, "w", newline="", encoding="utf-8") as f:
+        writer = csv.DictWriter(f, fieldnames=fieldnames)
+        writer.writeheader()
+        writer.writerows(order_rows)
+
+
+def write_synthesis_checklist(
+    order_rows: list[dict],
+    qc_results: list["SynthQC"],
+    out_path: str | Path,
+    generated_at: str = "",
+    panel_csv: str = "",
+) -> None:
+    """Write human-readable synthesis checklist markdown."""
+    out = Path(out_path)
+    out.parent.mkdir(parents=True, exist_ok=True)
+
+    n_total = len(order_rows)
+    n_acetyl = sum(1 for r in order_rows if r["n_modification"] == "Ac-")
+    n_amide = sum(1 for r in order_rows if r["c_modification"] == "NH2")
+    n_high = sum(1 for r in order_rows if r["synthesis_difficulty"] == "HIGH")
+    n_moderate = sum(1 for r in order_rows if r["synthesis_difficulty"] == "MODERATE")
+    n_low = sum(1 for r in order_rows if r["synthesis_difficulty"] == "LOW")
+    total_mg = sum(float(r["quantity_mg"]) for r in order_rows)
+
+    lines = [
+        "# Synthesis Order Checklist",
+        "",
+        "> Generated by `make synthesis-order`. Send this with the synthesis_order.csv to vendor.",
+        "",
+    ]
+    if generated_at:
+        lines += [f"Generated: {generated_at}  "]
+    if panel_csv:
+        lines += [f"Panel: {panel_csv}  "]
+    lines += [
+        f"Candidates: {n_total}",
+        "",
+        "## Order Summary",
+        "",
+        "| Metric | Value |",
+        "|---|---|",
+        f"| Total peptides | {n_total} |",
+        f"| N-terminal Ac- (acetylation) | {n_acetyl} |",
+        f"| C-terminal NH2 (amide) | {n_amide} |",
+        f"| Synthesis difficulty LOW | {n_low} |",
+        f"| Synthesis difficulty MODERATE | {n_moderate} |",
+        f"| Synthesis difficulty HIGH | {n_high} |",
+        f"| Total quantity ordered | {total_mg:.0f} mg |",
+        "",
+        "## Pre-Order Checklist",
+        "",
+        "- [ ] All sequences are standard L-amino acid one-letter codes",
+        "- [ ] HPLC purity spec confirmed as >95% for all candidates",
+        "- [ ] N-terminal Ac- candidates: confirm vendor accepts Nα-acetylation",
+        "- [ ] C-terminal NH2 candidates: confirm amide C-terminus included in quote",
+        f"- [ ] {n_high} HIGH-difficulty candidate(s): discuss yield with vendor before committing",
+        "- [ ] Cys-containing peptides: confirm inert-atmosphere synthesis and storage",
+        "- [ ] Trp-heavy peptides: confirm amber vial storage and red-light handling",
+        "- [ ] Request CoA (certificate of analysis) with HPLC trace and MS confirmation for each peptide",
+        "- [ ] Request minimum quantity as lyophilised powder (not solution)",
+        "",
+        "## Per-Candidate Order Details",
+        "",
+        "| # | ID | Seq (first 20 AA) | MW (Da) | N-term | C-term | Difficulty | Qty (mg) |",
+        "|--:|---|---|---:|:---:|:---:|:---:|---:|",
+    ]
+
+    for i, (row, qc) in enumerate(zip(order_rows, qc_results), 1):
+        seq_abbr = row["sequence"][:20] + ("…" if len(row["sequence"]) > 20 else "")
+        lines.append(
+            f"| {i} | {row['candidate_id']} | `{seq_abbr}` | {row['mol_weight_da']} "
+            f"| {row['n_modification']} | {row['c_modification']} "
+            f"| {row['synthesis_difficulty']} | {row['quantity_mg']:.0f} |"
+        )
+
+    lines += ["", "## Per-Candidate Handling Notes", ""]
+    for i, (row, qc) in enumerate(zip(order_rows, qc_results), 1):
+        lines += [f"### {i}. {row['candidate_id']} — `{row['sequence']}`", ""]
+
+        lines += [
+            f"- **MW:** {row['mol_weight_da']} Da | **pI:** {qc.isoelectric_point}",
+            f"- **Charge pH 7.4:** {qc.charge_ph74:.2f}",
+            f"- **N-modification:** {row['n_modification']}",
+            f"- **C-modification:** {row['c_modification']}",
+            f"- **Purity spec:** {row['purity_spec']}",
+            f"- **Quantity:** {row['quantity_mg']:.0f} mg",
+            f"- **Synthesis difficulty:** {row['synthesis_difficulty']}",
+        ]
+
+        if row["special_handling"]:
+            lines.append(f"- **Special handling:** {row['special_handling']}")
+
+        if qc.n_acetylation_recommended:
+            lines.append(f"- **N-Ac rationale:** {qc.n_acetylation_reason}")
+        if qc.c_amidation_recommended:
+            lines.append(f"- **C-amide rationale:** {qc.c_amidation_reason}")
+        if qc.wave2_d_substitutions:
+            lines.append("- **Wave 2 D-amino acid sites (future):**")
+            for s in qc.wave2_d_substitutions:
+                lines.append(f"  - {s}")
+
+        if qc.flags:
+            lines.append("- **QC flags:**")
+            for flag in qc.flags:
+                lines.append(f"  - ⚠ {flag}")
+        else:
+            lines.append("- **QC flags:** None")
+        lines.append("")
+
+    lines += [
+        "## Wave 2 D-Amino Acid Substitution Guide",
+        "",
+        "For any Wave 1 candidate with interior trypsin sites and demonstrated MIC ≤ 16 μg/mL:",
+        "",
+        "1. Identify the `wave2_d_substitutions` positions (listed per-candidate above).",
+        "2. Order D-Lys or D-Arg substituted variants from the same vendor.",
+        "3. Expected serum t½ improvement: 3–10× (Wade et al. 1990 PNAS).",
+        "4. Re-assay at same concentration range; compare MIC shift.",
+        "",
+        "## Disclaimer",
+        "",
+        "This checklist is computationally generated. QC flags are heuristic and do not",
+        "guarantee synthesis success or biological activity. Always request vendor review",
+        "for HIGH-difficulty sequences. No antimicrobial activity has been demonstrated",
+        "until wet-lab confirmation.",
+    ]
+
+    out.write_text("\n".join(lines) + "\n", encoding="utf-8")