19685-09-7

Basic information

• Product Name: 10-Hydroxycamptothecin
• Synonyms: Camptothecae Acuminatae extract;hydrate,(s)-dihydroxy;hydroxy-camptotheci;Hydroxycamptothencine;(20S)-10-HYDROXYCAMPTOTHECIN 98%;(20S)-10-Hydroxycamptothecin;HYDROCAMPTOTHECINE;CAMPTOTHECIN, 10-HYDROXY(SH)
• CAS NO: 19685-09-7
• Molecular Formula: C20H16N2O5
• Molecular Weight: 364.35
• EINECS: 2017-001-1
• Product Categories: Inhibitors;Alkaloids;INTERMEDIATESOFIRINOTECANHCLTRIHYDRATE;Camptothecin series;Natural Plant Extract;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Natural Anti-cancer Medical Materials and It's Derivatives;natural product
• Mol File: 19685-09-7.mol
• Article Data: 22

Chemical Properties

• Melting Point: 265-270°C
• Boiling Point: 820.7 °C at 760 mmHg
• Flash Point: 450.1 °C
• Appearance: Yellow solid
• Density: 1.60
• Vapor Pressure: 1.67E-28mmHg at 25°C
• Refractive Index: 1.776
• Storage Temp.: -20°C Freezer
• Solubility: ≥23.8 mg/mL in DMSO with gentle warming; insoluble in EtOH; insoluble in H2O
• PKA: 8.93±0.40(Predicted)
• CAS DataBase Reference: 10-Hydroxycamptothecin(CAS DataBase Reference)
• NIST Chemistry Reference: 10-Hydroxycamptothecin(19685-09-7)
• EPA Substance Registry System: 10-Hydroxycamptothecin(19685-09-7)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 19685-09-7(Hazardous Substances Data)

Usage

Uses

Used in Cancer Therapy:
10-Hydroxycamptothecin is used as a topoisomerase I inhibitor for cancer therapy. It targets the relaxation of DNA supercoiling by topoisomerase I at single-strand breaks, leading to the activation of apoptotic and cell cycle arrest pathways. This results in the inhibition of tumor growth and progression in various types of cancer.
Used in Pharmaceutical Industry:
10-Hydroxycamptothecin is used as an active pharmaceutical ingredient in the development of anticancer drugs. Its strong anti-tumor activity and less toxicity compared to the parent compound make it a valuable component in the formulation of cancer treatment medications.
Used in Research and Development:
10-Hydroxycamptothecin is used as a research compound in the study of topoisomerase I inhibitors and their potential applications in cancer therapy. It serves as a valuable tool for understanding the mechanisms of action and the development of novel anticancer agents.
Used in Drug Synthesis:
10-Hydroxycamptothecin is used as a key intermediate in the synthesis of various camptothecin-based anticancer drugs. Its unique chemical properties and strong anti-tumor activity make it an essential component in the development of new and effective cancer treatments.

in vitro

10-Hydroxycamptothecin inhibited the growth of BT-20 and MDA-231 cells with IC50 of 34.3nM and 7.27nM, respectively, which was more potent than camptothecin (CPT) with IC50>500nM. 10-Hydroxycamptothecin potently induces the formation of the pBR322 plasmid DNA cleavage complex mediated by human topoisomerase I with an EC50 of 0.35 μM, more than 50-fold more potent than CPT with an EC50 of 18.85 μM. 10-Hydroxycamptothecin treatment caused dose-dependent growth inhibition of human microvascular endothelial cells (HMECs) with IC50 of 0.31 μM and significantly inhibited HMEC migration with IC50 of 0.63 μM. Treatment of HMEC cells with 10-Hydroxycamptothecin also inhibited microtubule formation in a dose-dependent manner with IC50 of 0.96 μM. 10-Hydroxycamptothecin (5-20 nM) significantly inhibits the differentiation of Colo205 cells, arrests the cell cycle in G2 phase, and induces apoptosis through a caspase-3-dependent pathway.

in vivo

In the CAM model, 10-Hydroxycamptothecin treatment inhibited angiogenesis in a concentration-dependent manner, with 95% inhibition at 25 nM, more potent than suramin, which inhibited only 60% of angiogenesis at 125 nM. 10-Hydroxycamptothecin, administered orally at low doses of 2.5-7.5 mg/kg every two days, caused significant growth inhibition in Colo205 xenograft mice, but no acute toxicity. LD50: 104 mg/kg in mice (intraperitoneal injection).

IC 50

0.31 μm

references

[1] vladu b, woynarowski jm, manikumar g, wani mc, wall me, von hoff dd, wadkins rm. 7- and 10-substituted camptothecins: dependence of topoisomerase i-dna cleavable complex formation and stability on the 7- and 10-substituents. mol pharmacol. 2000 feb;57(2):243-51.[2] xiao d, tan w, li m, ding j. antiangiogenic potential of 10-hydroxycamptothecin. life sci. 2001 aug 24;69(14):1619-28. [3] ping yh, lee hc, lee jy, wu ph, ho lk, chi cw, lu mf, wang jj. anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer. oncol rep. 2006 may;15(5):1273-9.

InChI:InChI=1/C20H16N2O5/c1-2-20(26)14-7-16-17-11(5-10-6-12(23)3-4-15(10)21-17)8-22(16)18(24)13(14)9-27-19(20)25/h3-7,23,26H,2,8-9H2,1H3/t20-/m0/s1

Synthetic route

camptothecin (7689-03-4) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Stage #1: camptothecin With hydrogen; acetic acid; platinum(IV) oxide Stage #2: With lead(IV) acetate; acetic acid	51%
Yield given. Multistep reaction;
With sulfuric acid; dihydrogen peroxide; acetic acid 2) irradiation; Yield given. Multistep reaction;

10-methoxycamptothecin (19685-10-0) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
With hydrogen bromide at 110℃; for 72h;	82%
With hydrogen bromide In water at 110℃; for 7h; Inert atmosphere; optical yield given as %ee;	80%
With hydrogen bromide In water at 100℃; Sealed tube;	80%
With hydrogen bromide	72%
With hydrogen bromide In water for 2h; Reflux;

camptothecin (7689-03-4) → (S)-10-hydroxycamptothecin (19685-09-7) + (S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione (19685-11-1)

Conditions	Yield
Stage #1: camptothecin With hydrogen; acetic acid; platinum under 760.051 Torr; for 8.5h; Stage #2: With lead(IV) acetate In acetic acid Heating / reflux;

1,2,6,7-tetrahydro-(20S)-camphthotecine (870527-52-9) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
With [bis(acetoxy)iodo]benzene; water In acetic acid Yield given;
With [bis(acetoxy)iodo]benzene; acetic acid
In acetic acid at 20℃;
With [bis(acetoxy)iodo]benzene; acetic acid In water at 20℃; for 18h; Large scale reaction;	1.36 kg

tetrahydrocamptothecin acetate → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Stage #1: tetrahydrocamptothecin acetate With [bis(acetoxy)iodo]benzene In water; acetic acid at 27.5℃; for 18h; Stage #2: With methanol In N,N-dimethyl-formamide at 27.5 - 76.5℃; for 6h;

10-hydroxycamptothecin → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
In 1,4-dioxane; acetonitrile for 0.75h; UV-irradiation;	98.5%

9-<(dimethylamino)methyl>-10-hydroxy-(20S)-camptothecin acetate salt (123948-88-9) → (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-12-methylene-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione (942429-91-6) + (S)-10-hydroxycamptothecin (19685-09-7) + Topotecan hydrochloride (119413-54-6, 123949-07-5) + camptothecin (7689-03-4)

Conditions	Yield
With hydrogenchloride In water for 0.25h;	A < 0.04 %Chromat. B < 0.001 %Chromat. C 99.65 %Chromat. D < 0.009 %Chromat.

1,2,6,7-tetrahydrocamptothecin (53544-22-2, 142696-57-9, 142696-58-0) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 98 percent / pyridine / 1 h / 70 °C 2: 96.3 percent / H2SO4, conc. aq. HNO3 / 1 h 3: 82.3 percent / 20percent aq. H2SO4 / 2 h / Heating 4: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) / dioxane / 2 h / Heating 5: 96.2 percent / H2 / PtO2 / ethanol; dioxane / 2 h / 760 Torr 6: 1.) 20percent aq. H2SO4, aq. NaNO2, 2.) H2O / 1.) 0-5 deg C, 15 min, 2.) reflux, 1 h View Scheme
Multi-step reaction with 3 steps 1: 12 percent / Pb(OAc)4, trifluoroacetic acid / 0.25 h / Ambient temperature 2: 90.6 percent / 30percent aq. H2O2, acetic acid / 3.5 h / 70 - 80 °C 3: 22.5 percent / 1 N H2SO4 / dioxane / 0.5 h / Irradiation View Scheme
Multi-step reaction with 3 steps 1: 12 percent / Pb(OAc)4, trifluoroacetic acid / 0.25 h / Ambient temperature 2: 90.6 percent / 30percent aq. H2O2, acetic acid / 3.5 h / 70 - 80 °C 3: 25 percent / 1 N aq. H2SO4 / dioxane / 0.5 h / Irradiation View Scheme
Multi-step reaction with 3 steps 1: 12 percent / Pb(OAc)4, trifluoroacetic acid / 0.25 h / Ambient temperature 2: 90.6 percent / 30percent aq. H2O2, acetic acid / 3.5 h / 70 - 80 °C 3: 58 percent / 1 N aq. H2SO4 / dioxane / 0.5 h / Irradiation View Scheme

2-[2,2-Dimethoxy-eth-(Z)-ylidene]-malonic acid benzyl ester methyl ester (161681-84-1) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: LDA / tetrahydrofuran / -78 up to -20 deg C 2: H2 / 5percent Pd/C / methanol 3: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 4: TFA / H2O; toluene 5: DDQ 6: diisobutylaluminum hydride (DIBAH) / CH2Cl2 7: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 8: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 8 steps 1: LDA / tetrahydrofuran / -78 up to -20 deg C 2: H2 / 5percent Pd/C / methanol 3: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 4: TFA / H2O; toluene 5: DDQ 6: diisobutylaluminum hydride (DIBAH) / CH2Cl2 7: NaBH4 / methanol 8: 72 percent / 48percent HBr View Scheme

2-[1-((2R,4S)-2-tert-Butyl-4-ethyl-5-oxo-[1,3]dioxolan-4-yl)-2,2-dimethoxy-ethyl]-malonic acid benzyl ester methyl ester → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: H2 / 5percent Pd/C / methanol 2: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 3: TFA / H2O; toluene 4: DDQ 5: diisobutylaluminum hydride (DIBAH) / CH2Cl2 6: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 7: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 7 steps 1: H2 / 5percent Pd/C / methanol 2: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 3: TFA / H2O; toluene 4: DDQ 5: diisobutylaluminum hydride (DIBAH) / CH2Cl2 6: NaBH4 / methanol 7: 72 percent / 48percent HBr View Scheme

(S)-4-ethyl-4-hydroxy-6-iodo-3-oxo-1H-pyrano[3,4-c]-8-pyridone (173442-34-7) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 78 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide / 1.) 0 deg C, 10 min; r.t., 15 min, 2.) toluene, 70 deg C, 20 h 2: 51 percent / Me6Sn2 / benzene / 5 h / 70 °C / Irradiation 3: 82 percent / aq. HBr / 72 h / 110 °C View Scheme
Multi-step reaction with 2 steps 1: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 2: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

(S)-4-ethyl-4-hydroxy-6-iodo-8-methoxy-1,4-dihydro-pyrano[3,4-c]pyridin-3-one (174092-79-6) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 73 percent / Me3SiCl, NaI / acetonitrile; H2O / 5 h / 65 °C 2: 78 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide / 1.) 0 deg C, 10 min; r.t., 15 min, 2.) toluene, 70 deg C, 20 h 3: 51 percent / Me6Sn2 / benzene / 5 h / 70 °C / Irradiation 4: 82 percent / aq. HBr / 72 h / 110 °C View Scheme
Multi-step reaction with 3 steps 1: 72 percent / aq. HI 2: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 3: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

Camptothecin 1-oxide (86639-48-7) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: 11.5 percent / 1 N aq. H2SO4 / dioxane / 0.5 h / Irradiation 2: H2, acetic acid / PtO2 / dioxane / 760 Torr 3: 98 percent / pyridine / 1 h / 70 °C 4: 96.3 percent / H2SO4, conc. aq. HNO3 / 1 h 5: 82.3 percent / 20percent aq. H2SO4 / 2 h / Heating 6: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) / dioxane / 2 h / Heating 7: 96.2 percent / H2 / PtO2 / ethanol; dioxane / 2 h / 760 Torr 8: 1.) 20percent aq. H2SO4, aq. NaNO2, 2.) H2O / 1.) 0-5 deg C, 15 min, 2.) reflux, 1 h View Scheme
Multi-step reaction with 3 steps 1: 11.5 percent / 1 N aq. H2SO4 / dioxane / 0.5 h / Irradiation 2: H2, acetic acid / PtO2 / dioxane / 760 Torr 3: 73.5 percent / Pb(OAc)4, trifluoroacetic acid / 0.25 h / Ambient temperature View Scheme

Camptothecin 1-oxide (86639-48-7) → (S)-10-hydroxycamptothecin (19685-09-7) + ((S)-4-Ethyl-4-hydroxy-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-ylsulfanyl)-acetic acid ethyl ester (86639-49-8)

Conditions	Yield
With sulfuric acid In 1,4-dioxane for 0.5h; Irradiation;	A 58% B 11.9%

10-nitro-(20S)-camptothecin (86639-62-5) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 96.2 percent / H2 / PtO2 / ethanol; dioxane / 2 h / 760 Torr 2: 1.) 20percent aq. H2SO4, aq. NaNO2, 2.) H2O / 1.) 0-5 deg C, 15 min, 2.) reflux, 1 h View Scheme

N,20-O-diacetyl-1,2,6,7-tetrahydrocamptothecin → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 96.3 percent / H2SO4, conc. aq. HNO3 / 1 h 2: 82.3 percent / 20percent aq. H2SO4 / 2 h / Heating 3: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) / dioxane / 2 h / Heating 4: 96.2 percent / H2 / PtO2 / ethanol; dioxane / 2 h / 760 Torr 5: 1.) 20percent aq. H2SO4, aq. NaNO2, 2.) H2O / 1.) 0-5 deg C, 15 min, 2.) reflux, 1 h View Scheme

Acetic acid (4R,5bS,11aS)-4-acetoxy-4-ethyl-9-nitro-3,13-dioxo-3,4,5b,11a,12,13-hexahydro-1H,11H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-6-yl ester → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 82.3 percent / 20percent aq. H2SO4 / 2 h / Heating 2: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) / dioxane / 2 h / Heating 3: 96.2 percent / H2 / PtO2 / ethanol; dioxane / 2 h / 760 Torr 4: 1.) 20percent aq. H2SO4, aq. NaNO2, 2.) H2O / 1.) 0-5 deg C, 15 min, 2.) reflux, 1 h View Scheme

(S)-4-ethyl-4-hydroxy-6-iodo-7-(prop-2-yn-1-yl)-1,7-dihydro-3H-pyrano[3,4-c]pyridino-3,8(4H)-dione (174092-80-9) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 51 percent / Me6Sn2 / benzene / 5 h / 70 °C / Irradiation 2: 82 percent / aq. HBr / 72 h / 110 °C View Scheme

→ (S)-10-hydroxycamptothecin (19685-09-7)

Conditions

Yield

Multi-step reaction with 5 steps 1: 45 percent / ICl / CCl4; CH2Cl2 / 48 h / Ambient temperature 2: 73 percent / Me3SiCl, NaI / acetonitrile; H2O / 5 h / 65 °C 3: 78 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide / 1.) 0 deg C, 10 min; r.t., 15 min, 2.) toluene, 70 deg C, 20 h 4: 51 percent / Me6Sn2 / benzene / 5 h / 70 °C / Irradiation 5: 82 percent / aq. HBr / 72 h / 110 °C View Scheme

2-methoxy-6-(trimethylsilyl)pyridine (170453-55-1) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 9 steps 1: tBuLi 2: nBuLi, I2 3: 63 percent / Et3SiH / trifluoroacetic acid 4: 69 percent / K2CO3, Bu4NBr / Pd(OAc)2 5: 1.) OsO4, (DHQD)2-Pyr, 2.) I2, CaCO3 6: 47 percent / ICl 7: 72 percent / aq. HI 8: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 9: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

2-Methoxy-6-trimethylsilanyl-pyridine-3-carbaldehyde (453518-21-3) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: nBuLi, I2 2: 63 percent / Et3SiH / trifluoroacetic acid 3: 69 percent / K2CO3, Bu4NBr / Pd(OAc)2 4: 1.) OsO4, (DHQD)2-Pyr, 2.) I2, CaCO3 5: 47 percent / ICl 6: 72 percent / aq. HI 7: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 8: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

4-iodo-2-methoxy-6-trimethylsilanyl-3-pyridinecarboxaldehyde (174092-75-2) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: 63 percent / Et3SiH / trifluoroacetic acid 2: 69 percent / K2CO3, Bu4NBr / Pd(OAc)2 3: 1.) OsO4, (DHQD)2-Pyr, 2.) I2, CaCO3 4: 47 percent / ICl 5: 72 percent / aq. HI 6: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 7: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

3-[((E)-But-2-enyl)oxymethyl]-4-iodo-2-methoxy-6-trimethylsilanyl-pyridine → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 69 percent / K2CO3, Bu4NBr / Pd(OAc)2 2: 1.) OsO4, (DHQD)2-Pyr, 2.) I2, CaCO3 3: 47 percent / ICl 4: 72 percent / aq. HI 5: 88 percent / NaH, LiBr / 1,2-dimethoxy-ethane; dimethylformamide 6: Me3SnSnMe3 / benzene / 70 °C / Irradiation View Scheme

(S)-4-ethyl-4-hydroxy-6-iodo-7-(prop-2-yn-1-yl)-1,7-dihydro-3H-pyrano[3,4-c]pyridino-3,8(4H)-dione (174092-80-9) + 4-isocyanophenol (162471-15-0) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
With hexamethyldistannane In benzene at 70℃; Irradiation;

Camptothecin 1-oxide (86639-48-7) + acetic acid (64-19-7) → (S)-10-hydroxycamptothecin (19685-09-7) + (S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione (19685-11-1)

Conditions	Yield
With sulfuric acid In 1,4-dioxane for 0.5h; Irradiation;	A 25% B 30.5%

7-Methoxy-1,3-dihydro-pyrrolo[3,4-b]quinoline-2-carboxylic acid methyl ester (161681-89-6) → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: 30percent HBr/HOAc / 12 h / 20 °C 2: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 3: TFA / H2O; toluene 4: DDQ 5: diisobutylaluminum hydride (DIBAH) / CH2Cl2 6: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 7: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 7 steps 1: 30percent HBr/HOAc / 12 h / 20 °C 2: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 3: TFA / H2O; toluene 4: DDQ 5: diisobutylaluminum hydride (DIBAH) / CH2Cl2 6: NaBH4 / methanol 7: 72 percent / 48percent HBr View Scheme

2-(Methoxycarbonyl-prop-2-ynyl-amino)-N-(4-methoxy-phenyl)-acetimidic acid methyl ester → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: acetonitrile / 50 °C 2: 30percent HBr/HOAc / 12 h / 20 °C 3: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 4: TFA / H2O; toluene 5: DDQ 6: diisobutylaluminum hydride (DIBAH) / CH2Cl2 7: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 8: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 8 steps 1: acetonitrile / 50 °C 2: 30percent HBr/HOAc / 12 h / 20 °C 3: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 4: TFA / H2O; toluene 5: DDQ 6: diisobutylaluminum hydride (DIBAH) / CH2Cl2 7: NaBH4 / methanol 8: 72 percent / 48percent HBr View Scheme

2-[1-((2R,4S)-2-tert-Butyl-4-ethyl-5-oxo-[1,3]dioxolan-4-yl)-2,2-dimethoxy-ethyl]-malonic acid monomethyl ester → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 2: TFA / H2O; toluene 3: DDQ 4: diisobutylaluminum hydride (DIBAH) / CH2Cl2 5: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 6: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 6 steps 1: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 2: TFA / H2O; toluene 3: DDQ 4: diisobutylaluminum hydride (DIBAH) / CH2Cl2 5: NaBH4 / methanol 6: 72 percent / 48percent HBr View Scheme

7-Methoxy-2,3-dihydro-1H-pyrrolo[3,4-b]quinoline; hydrobromide → (S)-10-hydroxycamptothecin (19685-09-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 2: TFA / H2O; toluene 3: DDQ 4: diisobutylaluminum hydride (DIBAH) / CH2Cl2 5: 1.) NaBH4; 2.) aq. NaOH / 1.) MeOH 6: 72 percent / 48percent HBr View Scheme
Multi-step reaction with 6 steps 1: 89 percent / 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole (HOBT), Et3N / tetrahydrofuran 2: TFA / H2O; toluene 3: DDQ 4: diisobutylaluminum hydride (DIBAH) / CH2Cl2 5: NaBH4 / methanol 6: 72 percent / 48percent HBr View Scheme

diazomethane (186581-53-3, 908094-01-9) + (S)-10-hydroxycamptothecin (19685-09-7) → 10-methoxycamptothecin (19685-10-0)

Conditions	Yield
In 1,4-dioxane; methanol at 20℃; for 2h;	100%
	88%
In 1,4-dioxane; methanol; diethyl ether for 1h; Ambient temperature;	87.5%

(S)-10-hydroxycamptothecin (19685-09-7) + 4-piperidinopiperidine-1-carbonyl chloride (103816-19-9) → 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (103816-16-6)

Conditions	Yield
With pyridine In dichloromethane at 20℃; for 4h;	100%

(S)-10-hydroxycamptothecin (19685-09-7) → 9-bromo-10-hydroxycamptothecin (1097323-11-9)

Conditions	Yield
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	98%
With N-Bromosuccinimide In N,N-dimethyl-formamide	95%

N,N-phenylbistrifluoromethane-sulfonimide (37595-74-7) + (S)-10-hydroxycamptothecin (19685-09-7) → 10-hydroxy-(20S)-camptothecin trifluoromethanesulfonate (123949-09-7)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 23 - 50℃; Inert atmosphere;	97%
With triethylamine In N,N-dimethyl-formamide at 23 - 50℃;	97%
With triethylamine In N,N-dimethyl-formamide at 20℃;	96.7%
With triethylamine In N,N-dimethyl-formamide at 50℃; for 3h;
With triethylamine In N,N-dimethyl-formamide at 50℃;

(S)-10-hydroxycamptothecin (19685-09-7) → 9-iodine-10-hydroxycamptothecin (1256544-04-3)

Conditions	Yield
With N-iodo-succinimide In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	97%
With N-iodo-succinimide In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	95%

1-chlorocarbonyl-4-piperidinopiperidine hydrochloride + (S)-10-hydroxycamptothecin (19685-09-7) → 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin hydrochloride

Conditions	Yield
With potassium carbonate; triethylamine In acetonitrile at 60℃; for 6h;	97%

glutaric anhydride, (108-55-4) + (S)-10-hydroxycamptothecin (19685-09-7) → C25H22N2O8

Conditions	Yield
With pyridine at 25℃; for 72h;	97%

(S)-10-hydroxycamptothecin (19685-09-7) + 2-Methylpropionic anhydride (97-72-3) → camptothecin 10,20-di-O-isobutyrate

Conditions	Yield
sulfuric acid at 20 - 100℃; for 16h;	96%

(S)-10-hydroxycamptothecin (19685-09-7) → 10-hydroxy-mappicine ketone

Conditions	Yield
In various solvent(s) at 200℃; for 9h;	95%

triethylsilyl chloride (994-30-9) + (S)-10-hydroxycamptothecin (19685-09-7) → 20(S)-O-triethylsilylcampothecin (1004265-03-5)

Conditions	Yield
Stage #1: (S)-10-hydroxycamptothecin With 1H-imidazole In N,N-dimethyl-formamide for 0.166667h; Inert atmosphere; Stage #2: triethylsilyl chloride With dmap In N,N-dimethyl-formamide	94%
Stage #1: (S)-10-hydroxycamptothecin With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: triethylsilyl chloride With dmap In N,N-dimethyl-formamide at 20℃; for 60h; Inert atmosphere;	94%
With 1H-imidazole; dmap In N,N-dimethyl-formamide for 24.1667h;	94%

di-tert-butyl dicarbonate (24424-99-5) + (S)-10-hydroxycamptothecin (19685-09-7) → 10-tert-butoxycarbonyloxycamptothecin (362496-88-6)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide at 20℃;	94%
With pyridine In N,N-dimethyl-formamide at 20℃;
With pyridine In N,N-dimethyl-formamide at 20℃;	2.1 g
With pyridine In dichloromethane
In pyridine; N,N-dimethyl-formamide at 20℃; Inert atmosphere;

glutaric anhydride, (108-55-4) + (S)-10-hydroxycamptothecin (19685-09-7) → C25H22N2O8 (1353778-70-7)

Conditions	Yield
With pyridine at 20℃; for 48h;	94%
With pyridine at 20℃;	59.22%

(S)-10-hydroxycamptothecin (19685-09-7) + 4-Nitrophenyl chloroformate (7693-46-1) → 4-nitrophenyl camptothecin-10-yl carbonate (656233-42-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 1h; Schlenk technique;	93%
With triethylamine In tetrahydrofuran at 0 - 20℃; for 1h;	93%
With triethylamine at 20℃; for 1h;	91%

+ (S)-10-hydroxycamptothecin (19685-09-7) → C39H50N4O12 (945867-58-3)

Conditions	Yield
With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h;	92%

(S)-10-hydroxycamptothecin (19685-09-7) + Cyclohexanecarboxylic acid → (S)-4-ethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinolin-9-yl cyclohexanecarboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	92%

+ (S)-10-hydroxycamptothecin (19685-09-7) → Topotecan hydrochloride (119413-54-6, 123949-07-5)

Conditions	Yield
In propan-1-ol; dichloromethane	91%

formaldehyd (50-00-0) + (S)-10-hydroxycamptothecin (19685-09-7) + (S)-1-Pyrrolidin-2-yl-methanol → 10-hydroxyl-9-L-prolinol (+)methylcamptothecin (1439356-77-0)

Conditions	Yield
In acetic acid at 40 - 90℃; Mannich Aminomethylation;	90.2%

methanol (67-56-1) + (S)-10-hydroxycamptothecin (19685-09-7) → 7-hydroxymethyl-10-hydroxycamptothecin (86639-61-4)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide; iron(II) sulfate at 20℃; for 96h; hydroxymethylation;	90%

2-(hydroxymethyl)-1H-isoindole-1,3(2H)-dione (118-29-6) + (S)-10-hydroxycamptothecin (19685-09-7) → C29H21N3O7 (1352172-54-3)

Conditions	Yield
With sulfuric acid at 0 - 20℃; for 12h;	90%

N-hydroxymethyl-3,4,5,6-tetrahydrophthalimide (4887-42-7) + (S)-10-hydroxycamptothecin (19685-09-7) → C29H25N3O7 (1352172-55-4)

Conditions	Yield
With sulfuric acid at 0 - 20℃; for 12h;	90%

(S)-10-hydroxycamptothecin (19685-09-7) + prenyl bromide (870-63-3) → (S)-4-ethyl-4-hydroxy-9-((3-methylbut-2-en-1-yl)oxy)-1,12-dihydro-14H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione

Conditions	Yield
With potassium carbonate In acetone for 3h; Reflux;	90%

(S)-10-hydroxycamptothecin (19685-09-7) + chloroformic acid ethyl ester (541-41-3) → carbonic acid 4-ethoxycarbonyloxy-4-ethyl-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester ethyl ester

Conditions	Yield
With pyridine In 1,2-dichloro-ethane	89.2%

(S)-10-hydroxycamptothecin (19685-09-7) + poly(ethylene glycol)-O-glycolic acid ether → 10-camptothecin-[poly(ethylene glycol)-O-glycolic acid ether] ester, Mw=40000

Conditions	Yield
With pyridine; O-phenyl phosphorodichloridate In chloroform at 20℃; for 18h;	89%

C21H38N2O8 (945867-57-2) + (S)-10-hydroxycamptothecin (19685-09-7) → C41H54N4O13 (945867-59-4)

Conditions	Yield
With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h;	89%

butanoic acid anhydride (106-31-0) + (S)-10-hydroxycamptothecin (19685-09-7) → camptothecin 10,20-di-O-butyrate

Conditions	Yield
sulfuric acid at 20 - 100℃;	89%

1,3,6,9,12-pentaoxa-2-thiacyclotetradecane 2,2-dioxide + (S)-10-hydroxycamptothecin (19685-09-7) → C28H32N2O9

Conditions	Yield
Stage #1: 1,3,6,9,12-pentaoxa-2-thiacyclotetradecane 2,2-dioxide; (S)-10-hydroxycamptothecin With potassium carbonate In N,N-dimethyl-formamide at 40℃; Stage #2: With sulfuric acid In tetrahydrofuran; water for 3h; Reflux;	89%

(S)-10-hydroxycamptothecin (19685-09-7) + allyl bromide (106-95-6) → 10-allyloxycamptothecin (185425-24-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	88.2%
With potassium carbonate In N,N-dimethyl-formamide

C10H20O8S + (S)-10-hydroxycamptothecin (19685-09-7) → C30H36N2O10

Conditions	Yield
Stage #1: C10H20O8S; (S)-10-hydroxycamptothecin With potassium carbonate In N,N-dimethyl-formamide at 40℃; Stage #2: With sulfuric acid In tetrahydrofuran; water for 3h; Reflux;	88%

C18H36O12S + (S)-10-hydroxycamptothecin (19685-09-7) → C38H52N2O14

Conditions	Yield
Stage #1: C18H36O12S; (S)-10-hydroxycamptothecin With potassium carbonate In N,N-dimethyl-formamide at 40℃; Stage #2: With sulfuric acid In tetrahydrofuran; water for 3h; Reflux;	88%

Upstream product

• 86639-48-7 Camptothecin 1-oxide 
• 64-19-7 acetic acid 
• 53544-22-2 1,2,6,7-tetrahydrocamptothecin 
• 623-51-8 ethyl 2-sulfanylacetate 
• 7689-03-4 camptothecin 
• 19685-10-0 10-methoxycamptothecin 
• 1353579-41-5 (S)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-1-(3-(hydroxymethyl)-2-methoxypyridin-4-yl)propan-1-ol 
• 1353579-43-7 4-((S)-1-(benzyloxy)-1-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-propyl)-3-((benzyloxy)methyl)-2-methoxypyridine 
• 1353579-45-9 (2R,3S)-3-(benzyloxy)-3-(3-((benzyloxy)methyl)-2-methoxypyridin-4-yl)pentane-1,2-diol 
• 1201830-88-7 (S)-2-(benzyloxy)-2-(3-((benzyloxy)methyl)-2-methoxypyridin-4-yl)butanal 
• 1201830-89-8 (S)-2-(benzyloxy)-2-(3-((benzyloxy)methyl)-2-methoxypyridin-4-yl)butanoic acid 
• 16498-81-0 2-methoxynicotinic acid 
• 146683-25-2 4(S)-4-ethyl-4-hydroxy-4,7-dihydro-1H-pyrano<3,4-c>pyridin-3,8-dione 
• 158669-24-0 (S)-4-ethyl-4-hydroxy-8-methoxy-1H-pyrano[3,4-c]pyridin-3(4H)-one 

Downstream Products

• 123949-01-9 9-ethoxymethyl-10-hydroxy-(20S)-camptothecin 
• 104267-73-4 9-nitro-10-hydroxy-20(S)-camptothecin 
• 130064-60-7 9-<(cyclohexylamino)methyl>-10-hydroxy-(20S)-camptothecin acetate salt 
• 123949-02-0 10-hydroxy-9-[(N-methylanilino)methyl]-(20S)-camptothecin 
• 19685-10-0 10-methoxycamptothecin 
• 123948-87-8 topotecan 
• 656233-42-0 4-nitrophenyl camptothecin-10-yl carbonate 
• 86639-52-3 7-ethyl-10-hydroxycamptothecin 
• 1018932-85-8 10-[4-(2,3,4-tri-O-acetyl-6-O-methyl-β-D-glucuronyloxy)-3-nitrobenzyloxy]camptothecin 
• 1056470-85-9 C₂₈H₂₃N₃O₅ 
• 1056470-82-6 C₂₉H₂₅N₃O₅ 
• 1056470-78-0 C₂₉H₂₄FN₃O₅ 
• 1056470-79-1 C₃₀H₂₇N₃O₆ 
• 1056470-80-4 C₂₉H₂₅N₃O₅ 

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Relevant articles and documents

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A convergent protecting group-free total synthesis route of camptothecin and 10-hydroxycamptothecin has been developed in this work. Cascade oxidation of 3-(hydroxymethyl)furan-2(5 H)-one and in situ intermolecular oxa Diels-Alder reaction with vinyl ether was developed and applied to construct the E-ring, and TMSCl-promoted cascade closure of the D-ring delivered the whole skeleton of the alkaloids in the total synthesis. The new short syntheses were advantageous with regard to step economy, low cost, easily available starting materials and reagents, and convenient operations.

Expeditious total syntheses of camptothecin and 10-hydroxycamptothecin

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Synthesis of 10-hydroxycamptothecin: Evaluation of new moderators for the chemoselective reduction of camptothecin

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Chemical semi-synthesis process of 10-hydroxycamptothecine

The invention discloses a chemical semi-synthesis process of 10-hydroxycamptothecine. The chemical semi-synthesis process is characterized in that 20(S)-camptothecin, which is used as the raw material, is subjected to optimized N-oxidation and photochemical rearrangement reaction, and the product is subjected to silica gel column chromatography, so that high-purity 10-hydroxycamptothecine can be obtained. The chemical semi-synthesis process is simple and convenient in process conditions, the reaction reagent can be recycled, the production cost is low, the yield of 10-hydroxycamptothecine products is high, and the product is liable to separation, and accords with the national drug testing standard with the purity of 98.5%.

Total synthesis of camptothecin and SN-38

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Benzyl ether-linked glucuronide derivative of 10-hydroxycamptothecin designed for selective camptothecin-based anticancer therapy

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PROCESS FOR PREPARING IRINOTECAN

The present invention relates to a process for the preparation of pure irinotecan or salts thereof, and a process for the preparation of intermediate compound 7-ethyl-10-hydroxycamptothecin.

PROCESS FOR PREPARING TOPOTECAN

A process for preparing topotecan.

A practical regiospecific synthesis of 9-nitrocamptothecin

9-Nitrocamptothecin has shown potent antitumor activity against many types of human cancers. A practical scale-up procedure for this compound is reported by selective reduction of corresponding sulfonate. Georg Thieme Verlag Stuttgart.