73573-88-3

Basic information

• Product Name: Mevastatin
• Synonyms: Butanoic acid, 2-methyl-, (1S,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-7-methyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester, (2S)-;Mevastatin, >=97%;ML-236B;,8-beta(2s*,4s*),8a-beta))-;antibioticml236b;butanoicacid,2-methyl-,1,2,3,7,8,8a-hexahydro-7-methyl-8-(2-(tetrahydro-4-hy;compactin(penicillium);droxy-6-oxo-2h-pyran-2-yl)ethyl)-1-naphthalenylester,(1s-(1-alpha(r*),7-beta
• CAS NO: 73573-88-3
• Molecular Formula: C₂₃H₃₄O₅
• Molecular Weight: 390.51
• EINECS: 1312995-182-4
• Product Categories: Inhibitors;Active Pharmaceutical Ingredients;Various Metabolites and Impurities;Metabolites;Pharmaceuticals;HMG-CoA reductase;Intermediates & Fine Chemicals;Metabolites & Impurities;Cardiovascular APIs
• Mol File: 73573-88-3.mol
• Article Data: 18

Chemical Properties

• Melting Point: 151-153 °C
• Boiling Point: 555 °C at 760 mmHg
• Flash Point: 186.5 °C
• Appearance: white/powder
• Density: 1.13 g/cm³
• Vapor Pressure: 0Pa at 25℃
• Storage Temp.: 2-8°C
• Solubility: DMSO: 20 mg/mL
• PKA: 13.49±0.40(Predicted)
• Water Solubility: DMSO: 20 mg/mL
• Merck: 14,6164
• BRN: 1269441
• CAS DataBase Reference: Mevastatin(CAS DataBase Reference)
• NIST Chemistry Reference: Mevastatin(73573-88-3)
• EPA Substance Registry System: Mevastatin(73573-88-3)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28
• Safety Statements: 22-24/25-45-36/37/39
• WGK Germany: 3
• RTECS: EK7907100
• F: 1-8-10
• Hazardous Substances Data: 73573-88-3(Hazardous Substances Data)

Usage

Description

Mevastatin, also known as compactin, is a diterpene compound that belongs to the statin class of drugs. It is a potent competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Mevastatin is produced by several species of the genera Penicillium and Monascus and was first reported in 1976. It has various pharmacological properties, including inducing apoptosis, increasing eNOS mRNA and protein levels, inhibiting myoblast fusion, and inducing cell cycle arrest in the late G1 phase.

Uses

Used in Pharmaceutical Industry:
Mevastatin is used as an anti-hyperlipoproteinemic agent for lowering cholesterol levels in the blood. It functions as a 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor, which helps reduce the synthesis of cholesterol in the liver and subsequently lowers the levels of low-density lipoprotein (LDL) cholesterol in the bloodstream.
Used in Cardiovascular Applications:
Mevastatin is used as a cholesterol-lowering drug for the prevention and treatment of cardiovascular diseases, such as atherosclerosis, coronary artery disease, and stroke. By inhibiting HMG-CoA reductase, it reduces the production of cholesterol and helps maintain healthy blood vessels.
Used in Cancer Research:
Mevastatin is used as a research tool in cancer biology for studying the role of HMG-CoA reductase in cancer cell growth and proliferation. Its ability to induce apoptosis, cell cycle arrest, and inhibit protein prenylation makes it a valuable compound for investigating the molecular mechanisms underlying cancer development and progression.
Used in Cell Biology Research:
Mevastatin is used as a research tool in cell biology to study the role of HMG-CoA reductase in various cellular processes, such as myoblast fusion, cell cycle regulation, and protein prenylation. Its inhibitory effects on these processes provide insights into the molecular mechanisms that regulate cell growth, differentiation, and survival.

Biological Activity

Inhibitor of HMG-CoA reductase; decreases cholesterol biosynthesis, in vitro and in vivo . Induces apoptosis, arrests cancer cells in G1 phase and downregulates cdk 2, 4, and 6, cyclin D1 and E1, p21 and p27.

Biochem/physiol Actions

Mevastatin is a selective inhibitor of 3-hydroxy 3-methyl glutaryl coenzyme(A) reductase (HMG-CoA reductase), a major enzyme involved in cholesterol synthesis. It acts as a cholesterol-lowering agent. Mevastatin is obtained from various species of fungi. It acts as an antiresorptive?agent and has therapeutic effects to treat osteoporosis. Mevastatin inhibits bone resorption by triggering osteoclast apoptosis. It is also involved in the inhibition of prenylation of proteins such as Ras. Mevastatin increases endothelial nitric oxide synthase (eNOS) mRNA and protein levels by blocking the geranylgeranylation of transcription factor Rho.

Purification Methods

Purify compactin by recrystallisation from aqueous EtOH. UV (EtOH): max 230, 237 and 246nm (log  4.28, 4.30 and 4.11); IR (KBr): 3520, 1750 (lactone CO) and 1710 (CO ester) cm-1. [Clive et al. J Am Chem Soc 110 6914 1988, Review: Rosen & Heathcock Tetrahedron 42 4909 1986, IR, NMR, MS: Brown et al. J Chem Soc Perkin Trans 1 1165 1976.] It is a potent inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase), an enzyme in cholesterol biosynthesis, and lowers cholesterol levels [Brown et al. J Biol Chem 253 1121 1978, Nakamura & Ableles Biochemistry 24 1364 1985, Beilstein 18/3 V 145].

references

[1] endo a. the discovery and development of hmg-coa reductase inhibitors. journal of lipid research, 1992, 33(11): 1569-1582.

InChI:InChI:1S/C23H34O5/c1-4-14(2)23(26)28-20-7-5-6-16-9-8-15(3)19(22(16)20)11-10-18-12-17(24)13-21(25)27-18/h6,8-9,14-15,17-20,22,24H,4-5,7,10-13H2,1-3H3

Synthetic route

(1S,2S,8S,8aR,3'R,5'R,2''S)-methyl 1,2,6,7,8,8a-hexahydro-3',5'-dihydroxy-2-methyl-8-<(2-methyl-1-oxobutyl)oxy>-1-naphthaleneheptanoate (79814-60-1) → mevastatin (73573-88-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 1.08333h; Ambient temperature;	70%
With toluene-4-sulfonic acid In benzene	70%

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-[2-((2R,4R)-4,6-dihydroxy-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (116996-42-0, 117065-49-3) → mevastatin (73573-88-3)

Conditions	Yield
With Celite; silver carbonate In toluene at 95℃; for 2h;	61%

(1S,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-7-methyl-8-<2-((2R,4R)-tetrahydro-4-methoxy-6-oxo-2H-pyran-2-yl)-ethyl>-1-naphthyl (2S)-2-methylbutyrate (84751-53-1) → mevastatin (73573-88-3)

Conditions	Yield
With boron tribromide In dichloromethane at -23℃; for 5h;	31%
With boron tribromide In dichloromethane at -23℃; for 6h;	31%

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-diphenyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (108713-03-7) → mevastatin (73573-88-3)

Conditions	Yield
With hydrogen fluoride In water; acetonitrile at 45℃; for 8h;	30%

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (87000-71-3) → mevastatin (73573-88-3)

Conditions	Yield
With hydrogen fluoride In acetonitrile at 25℃; for 0.5h; Yield given;

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-[2-((2R,4R,6S)-4,6-dihydroxy-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (116996-42-0, 117065-49-3) → mevastatin (73573-88-3)

Conditions	Yield
With Celite; silver carbonate In toluene at 95℃; for 2h; Yield given;

3,5-Dihydroxy-7-[(1S,2S,8S,8aR)-2-methyl-8-((S)-2-methyl-butyryloxy)-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl]-heptanoic acid methyl ester (67383-81-7, 79814-60-1, 79896-19-8, 79896-20-1, 79896-21-2, 109785-25-3, 109785-26-4) → mevastatin (73573-88-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 25℃; for 0.5h;

(R)-3,5-Dihydroxy-7-[(1S,2S,8S,8aR)-2-methyl-8-((S)-2-methyl-butyryloxy)-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl]-heptanoic acid methyl ester (67383-81-7, 79814-60-1, 79896-19-8, 79896-20-1, 79896-21-2, 109785-25-3, 109785-26-4) → mevastatin (73573-88-3) + 3,5-bis-epi-compactin (84173-31-9)

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 25℃; for 0.25h;	A 32 mg B 22 mg

methyl 3,5-dihydroxy-7-<(1'S,2'S,8'S,8a'S)-2'methyl-8'-<(S)-2-methylbutanoyloxy>-1',2',3',7',8',8a'-hexahydro-1'-naphthyl>heptanoate (67383-81-7, 79814-60-1, 79896-19-8, 79896-20-1, 79896-21-2, 109785-25-3, 109785-26-4) → mevastatin (73573-88-3) + 3,5-bis-epi-compactin (84173-31-9)

Conditions	Yield
With pyridine hydrogenfluoride In acetonitrile at 0℃; for 6h;	A 15.6 mg B 15.4 mg

(4S,6R)-4-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-6-[2-((1S,2S,8aR)-2-methyl-8-triethylsilanyloxy-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl)-ethyl]-[1,3]dioxane (116996-36-2, 117065-47-1) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 2: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 3: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 4: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 5: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 6: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 7: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 8: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 8 steps 1: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 2: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 3: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 4: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 5: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 6: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 7: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 8: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

4-[(1S,5S,6S)-6-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-5-methyl-2-oxo-cyclohex-3-enyl]-4-triethylsilanyloxy-butyraldehyde (116996-35-1, 117065-46-0) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 3 h 2: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 3: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 4: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 5: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 6: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 7: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 8: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 9: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 9 steps 1: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 3 h 2: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 3: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 4: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 5: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 6: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 7: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 8: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 9: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(4R,6S)-6-(2-hydroxy-ethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (116996-40-8) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 2: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 3: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 3 steps 1: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 2: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 3: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(4R,6R)-2,2-dimethyl-6-(2-oxo-ethyl)-[1,3]dioxan-4-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (116996-41-9) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 2: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 2 steps 1: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 2: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

<4R-<4α*(1R*,2S*)>6α>>-6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-α-(2-methyl-5-oxo-3-cyclohexen-1-yl)-1,3-dioxane-4-propanal (116996-31-7, 126060-10-4) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 13 steps 1: 50 percent / (Ph3P)3RhCl / toluene; acetonitrile / 2.5 h / Heating 2: 1.) LDA / 1.) Et2O, -78 deg C, 1 h; 2.) -78 deg C, 10 min 3: 96 percent / i-Pr2NH / DMAP / diethyl ether / 36 h / Ambient temperature 4: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C, 20 min, r.t., 8 h 5: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 3 h 6: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 7: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 8: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 9: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 10: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 11: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 12: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 13: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 13 steps 1: 50 percent / (Ph3P)3RhCl / toluene; benzonitrile / 2.5 h / Heating 2: 1.) lithium diisopropylamide (LDA) / 1.) Et2O, -78 deg C, 1 h, 2.) -78 deg C, 10 min 3: 96 percent / i-Pr2NH, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 36 h / Ambient temperature 4: 1.) O3, 2.) Ph3P / 1.) CH2Cl2, -78 deg C, 20 min, 2.) RT, 8 h 5: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 3 h 6: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 7: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 8: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 9: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 10: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 11: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 12: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 13: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-3,7,8,8a-tetrahydro-2H-naphthalen-1-one (116996-38-4) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 2: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 3: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 4: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 5: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 6: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 6 steps 1: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 2: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 3: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 4: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 5: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 6: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(4S,5S,6S)-5-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-6-(1-hydroxy-pent-4-enyl)-4-methyl-cyclohex-2-enone (116996-33-9, 117065-44-8) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 11 steps 1: 96 percent / i-Pr2NH / DMAP / diethyl ether / 36 h / Ambient temperature 2: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C, 20 min, r.t., 8 h 3: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 3 h 4: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 5: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 6: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 7: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 8: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 9: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 10: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 11: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 11 steps 1: 96 percent / i-Pr2NH, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 36 h / Ambient temperature 2: 1.) O3, 2.) Ph3P / 1.) CH2Cl2, -78 deg C, 20 min, 2.) RT, 8 h 3: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 3 h 4: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 5: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 6: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 7: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 8: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 9: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 10: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 11: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (116996-39-5) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 2: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 3: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 4: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 4 steps 1: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 2: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 3: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 4: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(4S,5S,6S)-5-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-4-methyl-6-(1-triethylsilanyloxy-pent-4-enyl)-cyclohex-2-enone (116996-34-0, 117065-45-9) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C, 20 min, r.t., 8 h 2: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 3 h 3: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 4: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 5: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 6: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 7: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 8: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 9: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 10: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 10 steps 1: 1.) O3, 2.) Ph3P / 1.) CH2Cl2, -78 deg C, 20 min, 2.) RT, 8 h 2: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 3 h 3: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 4: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 5: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 6: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 7: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 8: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 9: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 10: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

<4R-<4α(4R*,5R*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one (116996-32-8) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 12 steps 1: 1.) LDA / 1.) Et2O, -78 deg C, 1 h; 2.) -78 deg C, 10 min 2: 96 percent / i-Pr2NH / DMAP / diethyl ether / 36 h / Ambient temperature 3: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C, 20 min, r.t., 8 h 4: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 3 h 5: 1.) HF; 2.) 2-methoxypropene / 2.) pyridinium p-toluenesulfonate / 1.) H2O, MeCN, r.t., 1.75 h; 2.) CH2Cl2, 0 deg C, 40 min 6: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 7: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 8: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 9: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 10: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 11: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 12: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 12 steps 1: 1.) lithium diisopropylamide (LDA) / 1.) Et2O, -78 deg C, 1 h, 2.) -78 deg C, 10 min 2: 96 percent / i-Pr2NH, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 36 h / Ambient temperature 3: 1.) O3, 2.) Ph3P / 1.) CH2Cl2, -78 deg C, 20 min, 2.) RT, 8 h 4: 85 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 3 h 5: 1.) 48percent aq. HF, 2.) 2-methoxypropene, pyridinium p-toluenesulfonate / 1.) MeCN, RT, 1.75 h, 2.) CH2Cl2, 0 deg C, 40 min 6: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 7: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 8: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 9: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 10: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 11: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 12: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-ol (116996-37-3, 117065-48-2) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 1.) (COCl)2; 2.Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 15 min; 2.) -78 deg C, 5 min 2: 80 percent / L-Selectride / tetrahydrofuran / -78 deg C, 1 h; -43 deg C, 12 h 3: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 4: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 5: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 6: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 7: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 7 steps 1: 93 percent / (COCl)2, DMSO / CH2Cl2 / 0.25 h / -78 °C 2: 80 percent / L-Selectride / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -43 deg C, 12 h 3: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 4: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 5: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 6: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 7: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

<1S-<1α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,6,7,8,8a-hexahydro-7-methyl-1-naphthalenol (117065-48-2) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 99 percent / Et3N / DMAP / CH2Cl2 / 68 h / Ambient temperature 2: 92 percent / Bu4NF / tetrahydrofuran / 1.75 h / Ambient temperature 3: 1.) (COCl)2; 2.) Et3N / 1.) DMSO,CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 30 min 4: 88 percent / 1.3N HCl / tetrahydrofuran / 2 h / Ambient temperature 5: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme
Multi-step reaction with 5 steps 1: 99 percent / Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 68 h / Ambient temperature 2: 92 percent / Bu4N(1+)*F(1-) / tetrahydrofuran / 1.75 h / Ambient temperature 3: 91 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C 4: 88 percent / 10percent aq. HCl / tetrahydrofuran / 2 h / Ambient temperature 5: 61 percent / Ag2CO3/Celite / toluene / 2 h / 95 °C View Scheme

(R)-3-<(tert-butyldimethylsilyl)oxy>-6-(dimethoxyphosphinyl)-5-oxohexanoic acid (96555-55-4) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 92 percent / diethyl ether / 0.25 h / Ambient temperature 2: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 3: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 4: aq. HF / acetonitrile / 0.83 h / Ambient temperature 5: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 6: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 6 steps 2: LiCl/DBU / acetonitrile 3: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 4: HF / acetonitrile 5: NaBH4 / 0.5 h / -15 °C 6: 70 percent / p-TsOH / benzene View Scheme

(R)-6-(Dimethoxyphosphinyl)-3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-5-oxohexanoic acid, methylester (96555-58-7) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 2: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 3: aq. HF / acetonitrile / 0.83 h / Ambient temperature 4: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 5: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: LiCl/DBU / acetonitrile 2: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 3: HF / acetonitrile 4: NaBH4 / 0.5 h / -15 °C 5: 70 percent / p-TsOH / benzene View Scheme

(S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-formyl-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (96575-19-8) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 2: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 3: aq. HF / acetonitrile / 0.83 h / Ambient temperature 4: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 5: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: LiCl/DBU / acetonitrile 2: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 3: HF / acetonitrile 4: NaBH4 / 0.5 h / -15 °C 5: 70 percent / p-TsOH / benzene View Scheme

(3R,1'R)-methyl 1'-phenylethyl 3-hydroxypentanedioate (96575-20-1) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 9 steps 1: 1.) N-BuLi / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 deg C to RT 2: 84 percent / imidazole / CH2Cl2 / 8 h / Ambient temperature 3: H2 / 10percent Pd/C / diethyl ether / 2 h / 760 Torr / Ambient temperature 4: 92 percent / diethyl ether / 0.25 h / Ambient temperature 5: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 6: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 7: aq. HF / acetonitrile / 0.83 h / Ambient temperature 8: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 9: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 9 steps 1: 43 percent / tetrahydrofuran / 0.17 h / -78 °C 2: C3H4N2 3: H2 / Pd-C 5: LiCl/DBU / acetonitrile 6: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 7: HF / acetonitrile 8: NaBH4 / 0.5 h / -15 °C 9: 70 percent / p-TsOH / benzene View Scheme

(3R,1'R)-methyl 1'-phenylethyl 3-<(tert-butyldimethylsilyl)oxy>pentanedioate (96555-51-0) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 10 steps 1: 99 percent / aq. HF / acetonitrile / 1.25 h / Ambient temperature 2: 1.) N-BuLi / 1.) THF, hexane, -78 deg C, 15 min, 2.) THF, hexane, from -78 deg C to RT 3: 84 percent / imidazole / CH2Cl2 / 8 h / Ambient temperature 4: H2 / 10percent Pd/C / diethyl ether / 2 h / 760 Torr / Ambient temperature 5: 92 percent / diethyl ether / 0.25 h / Ambient temperature 6: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 7: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 8: aq. HF / acetonitrile / 0.83 h / Ambient temperature 9: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 10: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 10 steps 1: HF / acetonitrile 2: 43 percent / tetrahydrofuran / 0.17 h / -78 °C 3: C3H4N2 4: H2 / Pd-C 6: LiCl/DBU / acetonitrile 7: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 8: HF / acetonitrile 9: NaBH4 / 0.5 h / -15 °C 10: 70 percent / p-TsOH / benzene View Scheme

(R)-dimethyl <<4-<<(R)-phenylethoxy>carbonyl>-3-hydroxybutyryl>methyl>phosphonate (96555-53-2) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 8 steps 1: 84 percent / imidazole / CH2Cl2 / 8 h / Ambient temperature 2: H2 / 10percent Pd/C / diethyl ether / 2 h / 760 Torr / Ambient temperature 3: 92 percent / diethyl ether / 0.25 h / Ambient temperature 4: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 5: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 6: aq. HF / acetonitrile / 0.83 h / Ambient temperature 7: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 8: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 8 steps 1: C3H4N2 2: H2 / Pd-C 4: LiCl/DBU / acetonitrile 5: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 6: HF / acetonitrile 7: NaBH4 / 0.5 h / -15 °C 8: 70 percent / p-TsOH / benzene View Scheme

(R)-dimethyl <<3-<(tert-butyldimethylsilyl)oxy>-4-<<(R)-phenylethoxy>carbonyl>butyryl>methyl>phosphonate (96555-54-3) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: H2 / 10percent Pd/C / diethyl ether / 2 h / 760 Torr / Ambient temperature 2: 92 percent / diethyl ether / 0.25 h / Ambient temperature 3: 55 percent / LiCl, 1,8-diazabicyclo<5.4.0>undec-7-ene (DBU) / dimethylsulfoxide / 30 h / Ambient temperature 4: (Ph3P)3RhCl, Et3SiH / benzene / 0.58 h / 70 °C 5: aq. HF / acetonitrile / 0.83 h / Ambient temperature 6: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 7: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 7 steps 1: H2 / Pd-C 3: LiCl/DBU / acetonitrile 4: Et3SiH/(Ph3p)3ClRh / toluene / 65 °C 5: HF / acetonitrile 6: NaBH4 / 0.5 h / -15 °C 7: 70 percent / p-TsOH / benzene View Scheme

(1S,2S,8S,8aR,5'R,2''S)-methyl 1,2,6,7,8,8a-hexahydro-5'hydroxy-2-methyl-8-<(2-methyl-1-oxobutyl)oxy>-3'-oxo-1-naphthaleneheptanoate (96555-61-2) → mevastatin (73573-88-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 9.6 mg / NaBH4 / methanol / 0.45 h / -15 - -13 °C 2: 70 percent / p-TsOH*H2O / benzene / 1.08 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: NaBH4 / 0.5 h / -15 °C 2: 70 percent / p-TsOH / benzene View Scheme

mevastatin (73573-88-3) → pravastatin (81093-37-0, 81131-74-0)

Conditions	Yield
	85.4%
Product distribution / selectivity;

mevastatin (73573-88-3) → <1S-<1α(3R*,5S*),2α,8β,8aα>>-7-(1,2,6,7,8,8a-Hexahydro-8-hydroxy-2-methyl-1-naphthalenyl)-1,3,5-heptanetriol (161466-60-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 9h; Ambient temperature;	81%
With lithium aluminium tetrahydride In diethyl ether

mevastatin (73573-88-3) → 6-desmethylmonacolin J (58889-19-3)

Conditions	Yield
With lithium hydroxide for 24h; Heating;	75%
Multi-step reaction with 2 steps 1: aq. LiOH / 24 h / Heating 2: 30 mg / toluene / 1 h / Heating View Scheme

diazomethane (186581-53-3, 908094-01-9) + mevastatin (73573-88-3) → (1S,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-7-methyl-8-<2-((2R,4R)-tetrahydro-4-methoxy-6-oxo-2H-pyran-2-yl)-ethyl>-1-naphthyl (2S)-2-methylbutyrate (84751-53-1)

Conditions	Yield
In diethyl ether; water at 0℃;	38%

formic acid (64-18-6) + mevastatin (73573-88-3) → (S)-2-Methyl-butyric acid (1S,4S,6S,7R,8S,8aR)-4-chloro-6-formyloxy-8-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester (153079-18-6)

Conditions	Yield
With tert-butylhypochlorite In dichloromethane at -10℃; Product distribution; Mechanism; reactions 1 or 2 equiv. terc-BuOCl;
With tert-butylhypochlorite In dichloromethane at -10℃;

formic acid (64-18-6) + mevastatin (73573-88-3) → (S)-2-Methyl-butyric acid (1S,4S,5R,6S,7R,8S)-4,5-dichloro-6-formyloxy-8-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,4,5,6,7,8-octahydro-naphthalen-1-yl ester

Conditions	Yield
With tert-butylhypochlorite In dichloromethane at -10℃;

mevastatin (73573-88-3) → anhydrocompactin (84173-32-0)

Conditions	Yield
With potassium hydrogensulfate In N,N-dimethyl-formamide for 6h; Heating;	2.7 mg

tert-butoxy radical (3141-58-0) + mevastatin (73573-88-3) → acetone (67-64-1) + tert-butyl alcohol (75-65-0)

Conditions	Yield
In acetonitrile at 40℃; for 15h; Kinetics; Product distribution;

mevastatin (73573-88-3) → (3R,5R)-3,5-Dihydroxy-7-((1S,2S,8S,8aR)-8-hydroxy-2-methyl-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl)-heptanoic acid

Conditions	Yield
With lithium hydroxide for 24h; Heating;

ethanol (64-17-5) + mevastatin (73573-88-3) → 3,5-dihydroxy-7-[2-methyl-8-(2-methyl-butyryloxy)-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl]-heptanoic acid ethyl ester

Conditions	Yield
With potassium hydroxide

mevastatin (73573-88-3) → (S)-2-Methyl-butyric acid (1S,4S,6S,7R,8S,8aR)-4-chloro-6-formyloxy-8-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester (153079-18-6)

mevastatin (73573-88-3) → Acetic acid (1S,7S,8S,8aR)-7-methyl-8-((3R,5S)-3,5,7-triacetoxy-heptyl)-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether 2: pyridine, DMAP View Scheme

mevastatin (73573-88-3) → <4R-<4α(4R*,5R*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one (116996-32-8)

Conditions	Yield
Multi-step reaction with 14 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 79 percent / LDA, Et3N / 0.42 h / -78 °C 10: 1.) m-CPBA, 2.) Bu4NF, AcOH 11: AcOH / methanol / 11 h 12: PPTS / 7.5 h 13: aq. NaIO4 / methanol / 23 h / Ambient temperature 14: PPTS / 2.5 h View Scheme
Multi-step reaction with 13 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 1.) potassium bis(trimethylsilyl)amide, 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine, 2.) Bu4NF / 1.) THF, toluene, -78 deg C, 30 min; -78 deg C, 30 min, 2.) THF, 30 min 10: AcOH / methanol / 11 h 11: PPTS / 7.5 h 12: aq. NaIO4 / methanol / 23 h / Ambient temperature 13: PPTS / 2.5 h View Scheme

mevastatin (73573-88-3) → <1S-<1α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,6,7,8,8a-hexahydro-7-methyl-1-naphthalenol (117065-48-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C View Scheme

mevastatin (73573-88-3) → (4R,5R)-5-[(3R,5S)-7-(tert-Butyl-diphenyl-silanyloxy)-3,5-dihydroxy-heptyl]-4-methyl-cyclohex-2-enone

Conditions	Yield
Multi-step reaction with 13 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 79 percent / LDA, Et3N / 0.42 h / -78 °C 10: 1.) m-CPBA, 2.) Bu4NF, AcOH 11: AcOH / methanol / 11 h 12: PPTS / 7.5 h 13: aq. NaIO4 / methanol / 23 h / Ambient temperature View Scheme
Multi-step reaction with 12 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 1.) potassium bis(trimethylsilyl)amide, 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine, 2.) Bu4NF / 1.) THF, toluene, -78 deg C, 30 min; -78 deg C, 30 min, 2.) THF, 30 min 10: AcOH / methanol / 11 h 11: PPTS / 7.5 h 12: aq. NaIO4 / methanol / 23 h / Ambient temperature View Scheme

mevastatin (73573-88-3) → <1S-<1α(3R*,5S*),2α,8β,8aα>>-1<<(1,1-Dimethylethyl)diphenylsilyl>oxy>-7-(1,2,6,7,8,8a-hexahydro-8-hydroxy-2-methyl-1-naphthalenyl)-3,5-heptanediol (126060-27-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h View Scheme

mevastatin (73573-88-3) → <1aR-<1aα,4β,4aα,5α(4R*,6S*),6α>>-5-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1a,2,4,4a,5,6-hexahydro-6-methyl-3H-naphth<1,8a-b>oxiren-4-ol (161466-61-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature View Scheme

mevastatin (73573-88-3) → (4R,7S,8S,8aR)-8-[(3R,5S)-7-(tert-Butyl-diphenyl-silanyloxy)-3,5-dihydroxy-heptyl]-2,4,4a-trihydroxy-7-methyl-3,4,4a,7,8,8a-hexahydro-2H-naphthalen-1-one

Conditions	Yield
Multi-step reaction with 11 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 79 percent / LDA, Et3N / 0.42 h / -78 °C 10: 1.) m-CPBA, 2.) Bu4NF, AcOH 11: AcOH / methanol / 11 h View Scheme
Multi-step reaction with 10 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 1.) potassium bis(trimethylsilyl)amide, 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine, 2.) Bu4NF / 1.) THF, toluene, -78 deg C, 30 min; -78 deg C, 30 min, 2.) THF, 30 min 10: AcOH / methanol / 11 h View Scheme

mevastatin (73573-88-3) → <4R-<4α,7β,8β(4R*,6S*),8aβ>>-4-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-3,4,4a,7,8,8a-hexahydro-2,4,4a-trihydroxy-7-methyl-1(2H)naphthalenone

Conditions	Yield
Multi-step reaction with 12 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 79 percent / LDA, Et3N / 0.42 h / -78 °C 10: 1.) m-CPBA, 2.) Bu4NF, AcOH 11: AcOH / methanol / 11 h 12: PPTS / 7.5 h View Scheme
Multi-step reaction with 11 steps 1: 81 percent / LiAlH4 / tetrahydrofuran / 9 h / Ambient temperature 2: 92 percent / imidazole / dimethylformamide / 1 h 3: 89 percent / PPTS / CH2Cl2 / 0.17 h / 0 °C 4: 89 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 2 h / Ambient temperature 5: 1.) Li, CuCN / 1.) THF, 2.) THF, 4 h 6: 95 percent / NaHCO3, t-BuOOH, VO(acac)2 / benzene / 6 h / Ambient temperature 7: 84 percent / Et3N, DMAP / CH2Cl2 / 0.17 h / 0 °C 8: 98 percent / Pr4NRuO4, 4 Angstroem molecular sieves, 4-methylmorpholine N-oxide / CH2Cl2 / 6 h 9: 1.) potassium bis(trimethylsilyl)amide, 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine, 2.) Bu4NF / 1.) THF, toluene, -78 deg C, 30 min; -78 deg C, 30 min, 2.) THF, 30 min 10: AcOH / methanol / 11 h 11: PPTS / 7.5 h View Scheme

Upstream product

• 116996-36-2 (4S,6R)-4-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-6-[2-((1S,2S,8aR)-2-methyl-8-triethylsilanyloxy-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl)-ethyl]-[1,3]dioxane 
• 116996-35-1 4-[(1S,5S,6S)-6-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-5-methyl-2-oxo-cyclohex-3-enyl]-4-triethylsilanyloxy-butyraldehyde 
• 116996-40-8 (S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(4R,6S)-6-(2-hydroxy-ethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 
• 116996-41-9 (S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-{2-[(4R,6R)-2,2-dimethyl-6-(2-oxo-ethyl)-[1,3]dioxan-4-yl]-ethyl}-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 
• 116996-31-7 <4R-<4α*(1R^*,2S^*)>6α>>-6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-α-(2-methyl-5-oxo-3-cyclohexen-1-yl)-1,3-dioxane-4-propanal 
• 116996-38-4 (7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-3,7,8,8a-tetrahydro-2H-naphthalen-1-one 
• 116996-33-9 (4S,5S,6S)-5-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-6-(1-hydroxy-pent-4-enyl)-4-methyl-cyclohex-2-enone 
• 116996-39-5 (S)-2-Methyl-butyric acid (1S,7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 
• 116996-34-0 (4S,5S,6S)-5-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-4-methyl-6-(1-triethylsilanyloxy-pent-4-enyl)-cyclohex-2-enone 
• 116996-32-8 <4R-<4α(4R^*,5R^*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one 
• 116996-37-3 (7S,8S,8aR)-8-(2-{(4R,6S)-6-[2-(tert-Butyl-diphenyl-silanyloxy)-ethyl]-2,2-dimethyl-[1,3]dioxan-4-yl}-ethyl)-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-ol 
• 117065-48-2 <1S-<1α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,6,7,8,8a-hexahydro-7-methyl-1-naphthalenol 
• 79782-54-0 2-Methyl-butyric acid (1S,7S,8S,8aR)-8-(3-hydroxy-propyl)-7-methyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 
• 85737-81-1 (1R,4S,4aR,8aS)-4-(acetoxy)-1,2,3,4,4a,5,8,8a-octahydronaphthalen-1-yl acetate 

Downstream Products

• 67-64-1 acetone 
• 75-65-0 tert-butyl alcohol 
• 81131-70-6 pravastatin sodium salt 
• 81093-37-0 pravastatin 
• 161466-62-2 <1R-<1α,4α,4aβ,5β(4R*,6S*),6β,7β>>-5-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-7-(dimethylphenylsilyl)-1,2,3,4,4a,5,6,7-octahydro-6-methyl-1,4-naphthalenediol 
• 161466-61-1 <1aR-<1aα,4β,4aα,5α(4R*,6S*),6α>>-5-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1a,2,4,4a,5,6-hexahydro-6-methyl-3H-naphth<1,8a-b>oxiren-4-ol 
• 126060-27-3 <1S-<1α(3R*,5S*),2α,8β,8aα>>-1<<(1,1-Dimethylethyl)diphenylsilyl>oxy>-7-(1,2,6,7,8,8a-hexahydro-8-hydroxy-2-methyl-1-naphthalenyl)-3,5-heptanediol 
• 117065-48-2 <1S-<1α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-Dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,6,7,8,8a-hexahydro-7-methyl-1-naphthalenol 
• 116996-32-8 <4R-<4α(4R^*,5R^*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one 
• 58889-19-3 6-desmethylmonacolin J 

Relevant articles and documents

FED BATCH SOLID STATE FERMENTATION FOR THE PRODUCTION OF HMG-COA REDUCTASE INHIBITORS

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Total synthesis of both (+)-compactin and (+)-mevinolin. A general strategy based on the use of a special titanium reagent for dicarbonyl coupling

A strategy is described for stereocontrolled synthesis of hypocholesterolemic compounds, (+)-compactin and (+)-mevinolin, by an approach (Scheme II) based on 6, 7, 4-pentenal (9a), and (R)-3-methyl-4-pentenal (9b). The Evans asymmetric Diels-Alder technique was used (Scheme III) to prepare 13, which was converted into the cis ester 17. Chain extension, iodolactonization, and elimination of HI then gave optically pure 6. The homochiral epoxide 24, made (Scheme IV) from (S)-malic acid, was converted into 25 and then, by iodocarbonation, hydrolysis, and ketalization, into the iodo ketal 7. Evans asymmetric alkylation was used (Scheme V) to prepare 9b. Ozonolysis, ketalization, and reduction (LiAlH4) of 28 gave 31, which was transformed by Swern oxidation, Wittig methylenation, and acid hydrolysis into 9b. An optically pure intermediate (8), common to both syntheses, was assembled (Scheme VI) by alkylation of 6 with 7, reduction to a mixture of lactols, allylic oxidation, and decarbonylation. Aldol condensation (Scheme VII) of 8 with 4-pentenal, triethylsilylation, and ozonolysis gave the enone aldehydes 39, epimeric at C-1. A modified McMurry reaction requiring an excess of a reagent prepared from C8K and TiCl3 (2:1 molar ratio) in DME, produced the ethers 40, which were converted into (+)-compactin by appropriate modification of the oxygen functionality. The strategy is general and was applied with minor modifications (Scheme VIII) to the synthesis of (+)-mevinolin.