Natural-product chemistry — IUPAC Division III organic chemistry at the secondary-metabolite / biosynthetic-pathway grain. Foundations: (1) The isoprene rule (Ruzicka 1921 / 1953, 'biogenetic isoprene rule'): all terpenes are built by…
natural-product-chemistry
Isoprene rule: terpene C-counts are exact multiples of 5 (C5n)
Ruzicka's biogenetic isoprene rule (1921, formalised 1953): all terpenes are biosynthesised by head-to-tail coupling of C₅ isoprene units…
Polyketide biogenesis: acetate C₂ head-to-tail via PKS; C1/C2 parity
Polyketide biogenesis (Birch 1953, Staunton & Weissman 2001). Polyketide synthases (PKS) catalyse the iterative condensation of acetyl-CoA…
Baldwin's rules: 20 favored / 10 disfavored of 30 (n, mode, hyb) triples
Baldwin's rules (J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 734): empirical stereo-electronic preferences for ring-closure reactions,…
Terpene C-counts sum 10+15+20+25+30+40 = 140 = 5·28
Sympy-exact witness of the isoprene-rule arithmetic: the total carbon count across the canonical terpene classes (monoterpene C₁₀ through…
Polyketide n=5 parity: C1-count = C2-count = 5; Σ (-1)^(k+1) = 0
Sympy-exact witness of the polyketide C1/C2 parity identity on an n = 5 acetate-unit chain (2n = 10 carbons total). Setup: even positions…
Baldwin enumeration: |favored|=20, |disfavored|=10, total=30 = 5·2·3
Sympy-exact witness of the Baldwin-rules enumeration. Setup: build the full Cartesian product {3,4,5,6,7} × {exo, endo} × {tet, trig, dig}…
Wallach isoprene-rule classification framework: terpene C-count is a fixed integer multiple of 5 (n·C5)
Wallach 1887 isoprene rule / Ruzicka 1953 biogenetic isoprene rule: all terpenes are biosynthetically constructed from isoprene-unit (C5)…
Polyketide chain-extension framework: 1 acetyl (C2) + n malonyl (each adding C2) → C(2n+2) chain
Polyketide biosynthesis chain-extension arithmetic: each polyketide chain starts with an acetyl-CoA unit (C2) and is extended by n…
Shikimate-pathway aromatic biogenesis framework: Phe / Tyr / Trp aromatic-amino-acid ring classifier
Shikimate-pathway aromatic biogenesis: the chorismate-branch shunt produces the three aromatic amino acids Phe, Tyr, Trp, each carrying an…
Isoprene C5-unit count: mono=2, sesqui=3, di=4, tri=6 (exact integers from Wallach rule)
Integer C5-unit count per terpene class: mono = 2, sesqui = 3, di = 4, tri = 6. Canonical pins: four exact integers.
Polyketide chain length: 2·n + 2 carbons; n=1 → C4 (acetoacetate); n=3 → C8 (tetraketide)
Chain-length fingerprint: n = 1 → C4 (acetoacetate), n = 3 → C8 (tetraketide level). Canonical pins: 2·n + 2, 4, 8.
Shikimate aromatic-ring count: Phe=1, Tyr=1, Trp=2 (indole bicyclic, by Clar-sextet / NMR-current aromaticity)
Aromatic-ring count: Phe = 1, Tyr = 1, Trp = 2 (indole). Canonical pins: three exact integers.
Isoprene rule (Ruzicka 1939)
L Ruzicka 1939 (Nobel 1939) C5 isoprene-unit oligomerization: mono/sesqui/di/sester/triterpenes; modern HMG-CoA reductase target of statin…
Polyketide synthases
J W Cornforth 1953 acetate hypothesis + D Hopwood 1985 actinomycete PKS clusters; modular PKS-I (erythromycin) + iterative PKS-II…
Alkaloid biosynthesis
G Stork 1950s mannich-type C-N bond-forming; pyridoxal-PLP cofactor; Robinson-tropinone 1917 elegant biomimetic synthesis; modern…
Taxol (Wani-Wall 1971)
Wani-Wall 1971 isolation from Taxus brevifolia bark; Holton 1994 + Nicolaou 1994 total syntheses; Wallace 2014 BMS…
Artemisinin (Tu Youyou 1972)
Tu Youyou 1972 (Nobel 2015) Project 523; artemisinin from Artemisia annua; endoperoxide-bridge mechanism; ACT first-line antimalarial;…
BGC genomics (Medema 2011)
M Medema 2011 antiSMASH; modern atlas BiG-FAM / MIBiG; >50,000 BGCs sequenced; basis of microbiome-derived natural-product discovery.
Quinine (Woodward 1944)
R Woodward-W Doering 1944 quinine; modern WHO essential medicine + artemisinin-combo Tu-Youyou + total-synthesis education.
Taxol (Wani-Wall 1971)
M Wani-M Wall 1971 paclitaxel; modern semi-synthesis Holton 1994 + biosynthesis-elucidation Croteau + immune-checkpoint combo.
B12 (Woodward-Eschenmoser 1973)
R Woodward-A Eschenmoser 1973 vitamin-B12 total-synthesis; modern foundational text on convergent strategy + retrosynthetic mastery.
Erythromycin (Woodward 1981)
R Woodward 1981 + Toshima 1992 erythromycin; modern macrolide-resistance + ketolide telithromycin + 2024 next-gen ribocil.
Polyketide (Collie 1893)
J N Collie 1893 polyketide; modern Hopwood 1985 PKS + assembly-line + combinatorial-biosynthesis Khosla 2003.
Penicillin (Fleming 1928)
A Fleming 1928 (Nobel 1945) penicillin + Heatley 1941 mass-production; modern β-lactam + Sheehan total-synthesis 1957.