72962-43-7

Basic information

• Product Name: Brassinolide
• Synonyms: 5-ALPHA-CHOLESTANE-B-HOMO-7-OXA-24-BETA-METHYL-2-ALPHA, 3-ALPHA, 22-ALPHA, 23-ALPHA-TETROL-6-ONE;2-ALPHA,3-ALPHA,22R,23R,-TETRAHYDROXY-B-HOMO-7-OXA-5-ALPHA-ERGOSTAN-6-ONE;2-ALPHA,3-ALPHA,22R,23R-TETRADHYDROXY-24R-METHYL-B-HOMO-7-OXA-5-ALPHA-CHOLESTAN-6-ONE;(22R,23R,24R)-2-ALPHA,3-ALPHA,22,23-TETRAHYDROXY-24-METHYL-B-HOMO-7-OXA-5-ALPHA-CHOLESTAN-6-ONE;22R,23R,24R-2ALPHA,3ALPHA,22,28-TETRAHYDROXY-B-HOMO-7-OXA-5ALPHA-ERGOSTA-6-ONE;24R-BRASSINOLIDE;BRASSINOLIDE;BRASSINOLIDE, NATURAL
• CAS NO: 72962-43-7
• Molecular Formula: C₂₈H₄₈O₆
• Molecular Weight: 480.68
• Product Categories: Bio-Pesticide;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;fertilizer
• Mol File: 72962-43-7.mol

Chemical Properties

• Melting Point: 200-204?C
• Boiling Point: 633.716 °C at 760 mmHg
• Flash Point: 202.262 °C
• Appearance: white to off-white/
• Density: 1.142 g/cm³
• Vapor Pressure: 1.01E-18mmHg at 25°C
• Refractive Index: 1.535
• Storage Temp.: −20°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 14.27±0.70(Predicted)
• CAS DataBase Reference: Brassinolide(CAS DataBase Reference)
• NIST Chemistry Reference: Brassinolide(72962-43-7)
• EPA Substance Registry System: Brassinolide(72962-43-7)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 72962-43-7(Hazardous Substances Data)

Usage

Uses

Used in Agriculture:
Brassinolide is used as a plant growth regulator for enhancing plant growth, development, and stress resistance. It promotes cell elongation, division, and differentiation, leading to improved crop yields and quality.
Used in Plant Research:
Brassinolide is utilized as a research tool for studying plant growth and development, as well as for understanding the role of brassinosteroids in various plant processes, including Auxin signaling and water-transport properties of cell membranes in Arabidopsis thaliana.

Biological Activity

brassinolide is a plant growth regulator. plant growth regulators are naturally produced by plants and are critical for regulating their own growth. plant growth regulators act via modifying or controlling plant growth processes, such as leave and flower formation, stem elongation, as well as fruit development and ripening.

Biochem/physiol Actions

Brassinolide is a plant growth hormone that has been implicated in Auxin signaling. It has also been used for studying plant biosynthetic pathways.

in vitro

brassinolide induced the time and concentration-dependent cytotoxicity in pc-3 cells. the mode of such cell death appeared to be apoptosis predominately, as demonstrated by fluorescence, flow-cytometric analyses and transmission electron microscopes. moreover, caspase-3 activity was increased after brassinolide treatment obviously. western blot studies showed brassinolide treatment triggered a time-dependent decrease in the expression of bcl-2 [1].

in vivo

brassinolide had the similar function of reducing the blood glucose levels as phenformin, but without the dose-dependent manner. the blood glucose levels showed significant differences after brassinolide treatment with different doses (200, 100, and 50 mg/kg). these results indicated that brassinolide could reduce the blood glucose levels without toxicity [2].

references

[1] wu yd,lou yj. brassinolide, a plant sterol from pollen of brassica napus l., induces apoptosis in human prostate cancer pc-3 cells. pharmazie.2007 may;62(5):392-5.[2] chen shi-ping, he jia, wang qi-jing, wang jian-dong, ye yan-li, xian li-jian. effect of brassinolide on levels of blood glucose in alloxan—induced diabetes rats. acta metallurgica sinica, 2009,v26(03): 21-23

InChI:InChI=1/C28H48O6/c1-14(2)15(3)24(31)25(32)16(4)18-7-8-19-17-13-34-26(33)21-11-22(29)23(30)12-28(21,6)20(17)9-10-27(18,19)5/h14-25,29-32H,7-13H2,1-6H3/t15-,16+,17+,18?,19+,20+,21-,22+,23-,24-,25+,27-,28-/m1/s1

Synthetic route

2α,3α-22R,23R-tetraacetoxy-B-homo-7-oxa-24S-methyl-5α-cholestan-6-one (76987-58-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
With potassium hydroxide In methanol for 1h; Heating;	94%
With sodium hydroxide In methanol; water for 3h; Heating;	57%
With hydrogenchloride; methanol; potassium hydroxide 1.) reflux, 1 h, 2.) room temperature, 1 h; Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: NaOH 2: HCl View Scheme

(2R,3S,5S,8S,9S,10R,13S,14S,17R)-17-{(S)-1-[(4R,5R)-5-((S)-1,2-Dimethyl-propyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-ethyl}-2,3-dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-6-one (83066-72-2) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) + (22R,23R,24S)-2α,3α,22,23-tetrahydroxy-6-oxa-7a-homo-5α-campestan-7-one (146205-07-4)

Conditions	Yield
With trifluoroacetyl peroxide In dichloromethane at 22℃; for 1h;	A 74% B n/a

(2R,3S,5α,22R,23R,24S)-6,6-Ethylenedioxy-2,3-isopropylidenedioxyergostane-22,23-diol (91708-76-8) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
With trifluoroacetyl peroxide; trifluoroacetic acid In chloroform for 3h; Ambient temperature;	53%
Multi-step reaction with 3 steps 1: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 2: pyridine, N,N-dimethylaminopyridine View Scheme

3-dehydroteasterone (124853-28-7) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
With amalgamated zinc; osmium(VIII) oxide; chloro-trimethyl-silane; trifluoroacetyl peroxide; 4-methylmorpholine N-oxide 1.) THF, rt., 12 h; 2.) THF, aq. t-BuOH; 3.) CH2Cl2; Yield given. Multistep reaction;

castasterone (80736-41-0) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Yield given. Multistep reaction;
Multi-step reaction with 2 steps 1: pyridine, N,N-dimethylaminopyridine View Scheme

2,3,22,23-tetra-O-acetylcastasterone (77027-48-6) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Yield given. Multistep reaction;

Acetic acid (1R,2R,3S)-2-acetoxy-1-[(S)-1-((1R,3aS,3bS,6aS,8S,9R,10aR,10bS,12aS)-8,9-dihydroxy-10a,12a-dimethyl-6-oxo-hexadecahydro-5-oxa-benzo[3,4]cyclohepta[1,2-e]inden-1-yl)-ethyl]-3,4-dimethyl-pentyl ester (106315-18-8) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
With sodium hydroxide In methanol for 3h; Heating;	1.79 g

(1S,2R,4R,5S)-2-[(1R,3aS,4S,5S,7aS)-1-((1S,2R,3R,4S)-2,3-Dihydroxy-1,4,5-trimethyl-hexyl)-4-hydroxymethyl-7a-methyl-octahydro-inden-5-yl]-4,5-dihydroxy-2-methyl-cyclohexanecarboxylic acid → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
With hydrogenchloride

(1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-{(S)-1-[(4R,5R)-5-((S)-1,2-Dimethyl-propyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-ethyl}-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-one (111118-49-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) + (22R,23R,24S)-2α,3α,22,23-tetrahydroxy-6-oxa-7a-homo-5α-campestan-7-one (146205-07-4)

Conditions	Yield
Yield given. Multistep reaction. Yields of byproduct given;

(20S)-6,6-ethylenedioxy-2α,3α-isopropylidenedioxy-5α-pregnane-20-carbaldehyde (81481-15-4) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) n-BuLi, 2.) 30percent H2O2 / 1.) THF, -78 deg C, 3 h, 2.) acetic acid, room temperature, 15 h 2: 85 percent / Ti(O-iPr)4, (+)-L-diethyl tartrate, cumene hydroperoxide, 4 Angstroem MS / CH2Cl2 / 144 h / -25 °C 3: 82 percent / CuCN / diethyl ether / 1.) -78 deg C, 2 h, 2.) 0 deg C, 3 h 4: 53 percent / CF3CO3H, CF3CO2H / CHCl3 / 3 h / Ambient temperature View Scheme
Multi-step reaction with 8 steps 1: n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 2: 74.6 percent / 1.) triphenylphosphine, benzoic acid, diethyl azodicarboxylate; 2.) K2CO3 / 1.) THF, 5-10 deg C, 30 min; 2.) THF/methanol, reflux, 3 h 3: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 4: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 5: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 6: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 7: pyridine, N,N-dimethylaminopyridine View Scheme
Multi-step reaction with 7 steps 1: 26.93 g / n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 2: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 3: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 4: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 5: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 6: pyridine, N,N-dimethylaminopyridine View Scheme

(2α,3α,5α,22S,23E)-6,6-ethylenedioxy-2,3-isopropylidenedioxy-26,27-dinorcholest-23-en-22-ol (148705-11-7) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / Ti(O-iPr)4, (+)-L-diethyl tartrate, cumene hydroperoxide, 4 Angstroem MS / CH2Cl2 / 144 h / -25 °C 2: 82 percent / CuCN / diethyl ether / 1.) -78 deg C, 2 h, 2.) 0 deg C, 3 h 3: 53 percent / CF3CO3H, CF3CO2H / CHCl3 / 3 h / Ambient temperature View Scheme

(2R,3S,5α,22R)-23,24-epoxy-6,6-(ethylenedioxy)-2,3-(isopropylidenedioxy)-26,27-dinorcholestan-22-ol (223117-11-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / CuCN / diethyl ether / 1.) -78 deg C, 2 h, 2.) 0 deg C, 3 h 2: 53 percent / CF3CO3H, CF3CO2H / CHCl3 / 3 h / Ambient temperature View Scheme

3-methyl-butan-2-one (563-80-4) + ethyl halide → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 10 steps 1: Br2 / methanol 2: acetone / 18 h / Heating 3: NaH / tetrahydrofuran / 0.5 h / 25 °C 4: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 5: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 6: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 7: 96 percent / CSA / 24 h / Ambient temperature 8: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 9: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme
Multi-step reaction with 10 steps 1: Br2 / methanol 2: acetone / 18 h / Heating 3: 1.) NaH, triethylphosphonoacetate, 2.) aq. KOH / 1.) THF, 25 deg C, 30 min, 2.) 25 deg C, 24 h 4: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 5: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 6: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 7: 96 percent / CSA / 24 h / Ambient temperature 8: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 9: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

4-(1-methylethyl)furan-2(5H)-one (10547-89-4) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 7 steps 1: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 2: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 3: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 4: 96 percent / CSA / 24 h / Ambient temperature 5: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 6: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

1-(acetyloxy)-3-methyl-2-butanone (36960-07-3) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: NaH / tetrahydrofuran / 0.5 h / 25 °C 2: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 3: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 4: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 5: 96 percent / CSA / 24 h / Ambient temperature 6: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 7: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme
Multi-step reaction with 8 steps 1: 1.) NaH, triethylphosphonoacetate, 2.) aq. KOH / 1.) THF, 25 deg C, 30 min, 2.) 25 deg C, 24 h 2: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 3: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 4: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 5: 96 percent / CSA / 24 h / Ambient temperature 6: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 7: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(22E)-stigmasta-2,22-dien-6-one (74174-45-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 11 steps 1: 72 percent / OsO4, NMO, H2O / acetone; 2-methyl-propan-2-ol / 12 h / Ambient temperature 2: 98 percent / CSA / acetonitrile; CH2Cl2 / 1 h / Ambient temperature 3: OsO4, NMO, aq. NaHCO3, MeSO2NH2 / tetrahydrofuran; 2-methyl-propan-2-ol / 144 h / 40 °C 4: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 5: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 6: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 7: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 8: 96 percent / CSA / 24 h / Ambient temperature 9: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 10: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(22E,24S)-3β,5-cyclo-24-ethylcholest-22-en-6-one (74174-49-5) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 12 steps 1: 80 percent / pyridine hydrochloride, LiBr / N,N-dimethyl-acetamide / 4 h / 160 °C 2: 72 percent / OsO4, NMO, H2O / acetone; 2-methyl-propan-2-ol / 12 h / Ambient temperature 3: 98 percent / CSA / acetonitrile; CH2Cl2 / 1 h / Ambient temperature 4: OsO4, NMO, aq. NaHCO3, MeSO2NH2 / tetrahydrofuran; 2-methyl-propan-2-ol / 144 h / 40 °C 5: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 6: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 7: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 8: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 9: 96 percent / CSA / 24 h / Ambient temperature 10: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 11: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(22E,24S)-2α,3α-dihydroxy-5α-stigmast-22-en-6-one (81481-12-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 10 steps 1: 98 percent / CSA / acetonitrile; CH2Cl2 / 1 h / Ambient temperature 2: OsO4, NMO, aq. NaHCO3, MeSO2NH2 / tetrahydrofuran; 2-methyl-propan-2-ol / 144 h / 40 °C 3: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 4: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 5: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 6: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 7: 96 percent / CSA / 24 h / Ambient temperature 8: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 9: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(22E,24S)-2α,3α-Dihydroxy-5α-stigmast-22-en-6-one 2,3-acetonide (81481-13-2) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 9 steps 1: OsO4, NMO, aq. NaHCO3, MeSO2NH2 / tetrahydrofuran; 2-methyl-propan-2-ol / 144 h / 40 °C 2: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 3: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 4: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 5: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 6: 96 percent / CSA / 24 h / Ambient temperature 7: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 8: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme
Multi-step reaction with 10 steps 1: 83.0 g / p-TsOH / 3 h / Heating 2: 30 g / ozone, NaHCO3 / methanol; CH2Cl2 / 2 h / -60 - -50 °C 3: n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 4: 74.6 percent / 1.) triphenylphosphine, benzoic acid, diethyl azodicarboxylate; 2.) K2CO3 / 1.) THF, 5-10 deg C, 30 min; 2.) THF/methanol, reflux, 3 h 5: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 6: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 7: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 8: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 9: pyridine, N,N-dimethylaminopyridine View Scheme
Multi-step reaction with 9 steps 1: 83.0 g / p-TsOH / 3 h / Heating 2: 30 g / ozone, NaHCO3 / methanol; CH2Cl2 / 2 h / -60 - -50 °C 3: 26.93 g / n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 4: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 5: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 6: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 7: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 8: pyridine, N,N-dimethylaminopyridine View Scheme

(22E,24S)-24-ethyl-3α,5-cyclo-5α-cholest-22-en-6-ol (103881-47-6) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 13 steps 1: CrO3, H2SO4 / acetone 2: 80 percent / pyridine hydrochloride, LiBr / N,N-dimethyl-acetamide / 4 h / 160 °C 3: 72 percent / OsO4, NMO, H2O / acetone; 2-methyl-propan-2-ol / 12 h / Ambient temperature 4: 98 percent / CSA / acetonitrile; CH2Cl2 / 1 h / Ambient temperature 5: OsO4, NMO, aq. NaHCO3, MeSO2NH2 / tetrahydrofuran; 2-methyl-propan-2-ol / 144 h / 40 °C 6: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 7: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 8: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 9: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 10: 96 percent / CSA / 24 h / Ambient temperature 11: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 12: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

1-bromo-3-methyl-2-butanone (19967-55-6) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 9 steps 1: acetone / 18 h / Heating 2: NaH / tetrahydrofuran / 0.5 h / 25 °C 3: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 4: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 5: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 6: 96 percent / CSA / 24 h / Ambient temperature 7: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 8: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme
Multi-step reaction with 9 steps 1: acetone / 18 h / Heating 2: 1.) NaH, triethylphosphonoacetate, 2.) aq. KOH / 1.) THF, 25 deg C, 30 min, 2.) 25 deg C, 24 h 3: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 4: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 5: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 6: 96 percent / CSA / 24 h / Ambient temperature 7: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 8: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(20S)-2α,3α-isopropylidenedioxy-5α-pregnan-6-one-20-carbaldehyde (174656-33-8) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 7 steps 1: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 2: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 3: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 4: 96 percent / CSA / 24 h / Ambient temperature 5: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 6: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(3S,4R,5R,6S)-6-((1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-5-Hydroxy-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-1-yl)-3-isopropyl-heptane-1,4,5-triol → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 96 percent / CSA / 24 h / Ambient temperature 2: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 3: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-((S)-1-{(4R,5R)-5-[(S)-1-(2-Hydroxy-ethyl)-2-methyl-propyl]-2,2-dimethyl-[1,3]dioxolan-4-yl}-ethyl)-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-ol → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 2: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(S)-3-{(4R,5R)-2,2-Dimethyl-5-[(S)-1-((1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-8,8,10a,12a-tetramethyl-5-oxo-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-1-yl)-ethyl]-[1,3]dioxolan-4-yl}-4-methyl-pentanal (174656-38-3) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-((1S,2S,3S,4S)-4-Ethyl-2,3-dihydroxy-1,5-dimethyl-hexyl)-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-one (123450-38-4) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 8 steps 1: 82 percent / pyridine, NaHCO3, H5IO6 / tetrahydrofuran / 24 h / Ambient temperature 2: 80 percent / LDA / tetrahydrofuran / 1.) -40 to -50 deg C, 30 min, 2.) -75 deg C, 14 h 3: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 4: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 5: 96 percent / CSA / 24 h / Ambient temperature 6: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 7: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-[(1S,2R)-2-Hydroxy-2-((2R,3S)-3-isopropyl-5-oxo-tetrahydro-furan-2-yl)-1-methyl-ethyl]-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-one (174656-35-0) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 2: 96 percent / CSA / 24 h / Ambient temperature 3: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 4: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

(1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-[(1S,2R)-2-Hydroxy-2-((R)-3-isopropyl-5-oxo-2,5-dihydro-furan-2-yl)-1-methyl-ethyl]-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-one (174656-34-9) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions

Yield

Multi-step reaction with 6 steps 1: 83 percent / H2, pyridine / 10percent Pd/C / ethanol; tetrahydrofuran / 14 h / 2585.7 Torr / Ambient temperature 2: 99 percent / LAH / tetrahydrofuran / 1.) r.t. 2 h, 2.) reflux, overnight 3: 96 percent / CSA / 24 h / Ambient temperature 4: 91 percent / CrO3, pyridine / CH2Cl2 / 48 h / Ambient temperature 5: 72 percent / <(C6H5)3P>3RhCl / benzene / 5 h / Heating View Scheme

6,6-ethylenedioxy-2α,3α-isopropylidenedioxy-24S-ethyl-5α-cholest-22E-ene (81481-14-3) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 9 steps 1: 30 g / ozone, NaHCO3 / methanol; CH2Cl2 / 2 h / -60 - -50 °C 2: n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 3: 74.6 percent / 1.) triphenylphosphine, benzoic acid, diethyl azodicarboxylate; 2.) K2CO3 / 1.) THF, 5-10 deg C, 30 min; 2.) THF/methanol, reflux, 3 h 4: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 5: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 6: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 7: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 8: pyridine, N,N-dimethylaminopyridine View Scheme
Multi-step reaction with 8 steps 1: 30 g / ozone, NaHCO3 / methanol; CH2Cl2 / 2 h / -60 - -50 °C 2: 26.93 g / n-BuLi / tetrahydrofuran; hexane / -50 to -60 deg C; -40 deg C, 1 h; -68 to - 65 deg C, 1 h; 0 deg C 3: 44.3 g / H2, 1M NaBH4, ethylenediamine, nickel acetate / aq. ethanol / 5 h 4: 93 percent / m-chloroperbenzoic acid, Na2HPO4 / CH2Cl2 / 20 h / 5 °C 5: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 6: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 7: pyridine, N,N-dimethylaminopyridine View Scheme

(2R, 3S, 22R, 23S, 24R)-23,24-epoxy-6,6-ethylenedioxy-22-hydroxy-2,3-isopropylidenedioxy-5α-cholestane (86413-56-1) → (3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: n-BuLi / hexane; cyclohexane / -70 deg C, 1 h; 10 deg C, 4 h 2: 7.62 g / 80percent AcOH / H2O / 1 h / 50 - 60 °C 3: pyridine, N,N-dimethylaminopyridine View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) + acetic anhydride (108-24-7) → 2α,3α-22R,23R-tetraacetoxy-B-homo-7-oxa-24S-methyl-5α-cholestan-6-one (76987-58-1)

Conditions	Yield
With pyridine at 60℃; for 20h; Acetylation;	95%

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) + acetone (67-64-1) → C34H56O6 (220399-01-9)

Conditions	Yield
With toluene-4-sulfonic acid for 8h; Ambient temperature;	91%

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) + 2,2-dimethoxy-propane (77-76-9) → C34H56O6

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane Ambient temperature;	82%

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → Brassinolide + (1R,2R,4R,5S)-2-[(1R,3aS,4S,5S,7aS)-1-((1S,2R,3R,4S)-2,3-Dihydroxy-1,4,5-trimethyl-hexyl)-4-hydroxymethyl-7a-methyl-octahydro-inden-5-yl]-4-hydroxy-2-methyl-6-oxa-bicyclo[3.2.1]octan-7-one

Conditions	Yield
With methanol; Dowex 50W resin (H(1+)-form); water; sodium methylate 1.) reflux, 5 h, 2.) MeOH, r.t., 3 h; Yield given. Multistep reaction. Yields of byproduct given;

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 2,3,22,33-tetra-O-acetyl-25-hydroxybrassinolide (180961-17-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 61 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 5 h / -30 °C View Scheme
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 48 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 25-hydroxybrassinolide

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 61 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 5 h / -30 °C 3: 86 percent / KOH / methanol; H2O / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 61 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 5 h / -30 °C 3: 56 percent / KOH / methanol; H2O / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 48 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 86 percent / KOH / methanol; H2O / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 48 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 56 percent / KOH / methanol; H2O / 3 h / Heating View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 14α-hydroxybrassinolide

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 6.5 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 82 percent / KOH / methanol; H2O / 1 h / 20 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 25-hydroxy-6(6α->3a)abeo-5-epi-brassinolide

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 61 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 5 h / -30 °C 3: 12 percent / KOH / methanol; H2O / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 48 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 12 percent / KOH / methanol; H2O / 3 h / Heating View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 5-epi-25-hydroxybrassinolide

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 61 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 5 h / -30 °C 3: 22 percent / KOH / methanol; H2O / 3 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 48 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 22 percent / KOH / methanol; H2O / 3 h / Heating View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 14α,25-dihydroxybrassinolide

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 18 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C 3: 79 percent / KOH / methanol; H2O / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 78 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 24 h / 20 °C 3: 79 percent / KOH / methanol; H2O / 1 h / 20 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 2,3,22,33-tetra-O-acetyl-14α-hydroxybrassinolide

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 6.5 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 2,3,22,33-tetra-O-acetyl-25-hydroxy-15-oxo-brassinolide

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 3.6 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → 2,3,22,33-tetra-O-acetyl-14α,25-dihydroxybrassinolide (215502-60-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 18 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 3 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: 95 percent / pyridine / 20 h / 60 °C 2: 78 percent / methyl(trifluoromethyl)dioxirane; 1,1,1-trifluoroacetone / CH2Cl2 / 24 h / 20 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-22,23-isopropylidenedioxy-B-homo-7-oxa-5α-ergost-2-en-6-one (220398-86-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: 4-dimethylaminopyridine / CH2Cl2 / 2 h / 0 °C 4: triethyl phosphite / 5 h / Heating View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2α,3α-epoxy-22,23-isopropylidenedioxy-B-homo-7-oxa-5α-ergostan-6-one (220399-03-1)

Conditions	Yield
Multi-step reaction with 5 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: 4-dimethylaminopyridine / CH2Cl2 / 2 h / 0 °C 4: triethyl phosphite / 5 h / Heating 5: 50 percent / m-CPBA / CH2Cl2 / 2 h / 0 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2α,3α-dihydroxy-22,23-isopropylidenedioxy-B-homo-7-oxa-5α-ergostan-6-one (220398-85-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2α,3β-dihydroxy-22,23-isopropylidenedioxy-B-homo-7-oxa-5α-ergostan-6-one (220398-88-9)

Conditions	Yield
Multi-step reaction with 6 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: Et3N, DMAP / CH2Cl2 / 2 h / Ambient temperature 4: pyridinium dichromate, pyridine / 5 h / 70 °C 5: NaBH4 / tetrahydrofuran / 5 h / Ambient temperature 6: tetra-n-butylammonium fluoride / tetrahydrofuran / 1 h / Ambient temperature View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2β,3α,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one (220401-52-5)

Conditions	Yield
Multi-step reaction with 6 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: 4-dimethylaminopyridine / CH2Cl2 / 2 h / 0 °C 4: triethyl phosphite / 5 h / Heating 5: 50 percent / m-CPBA / CH2Cl2 / 2 h / 0 °C 6: 30 percent / aq. HClO4 / dioxane / 5 h / Ambient temperature View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2α,3β,22,23-tetrahydroxy-B-homo-7-oxa-5α-ergostan-6-one

Conditions

Yield

Multi-step reaction with 7 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: Et3N, DMAP / CH2Cl2 / 2 h / Ambient temperature 4: pyridinium dichromate, pyridine / 5 h / 70 °C 5: NaBH4 / tetrahydrofuran / 5 h / Ambient temperature 6: tetra-n-butylammonium fluoride / tetrahydrofuran / 1 h / Ambient temperature 7: 85 percent / 80 percent aq. AcOH / 2 h / 100 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → C32H50O6S

Conditions	Yield
Multi-step reaction with 3 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: 4-dimethylaminopyridine / CH2Cl2 / 2 h / 0 °C View Scheme

(3α,5α,6α,8β,9α,12β,13β,16α,17β)-10-[(2'α,3'β,4'β,5'β)-3,4-dihydroxy-5,6-dimethyl-2-heptanyl]-5,6-dihydroxy-7a,9a-dimethylhexadecahydro-3H-benzo[c]indeno[5,4-e]oxepin-3-one (72962-43-7) → (22R,23R,24S)-2α-t-butyldimethylsiloxy-22,23-isopropylidenedioxy-B-homo-7-oxa-5α-ergostan-3,6-dione (220398-87-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 91 percent / p-TsOH / 8 h / Ambient temperature 2: 86 percent / aq. p-TsOH / dioxane / 4 h / 60 °C 3: Et3N, DMAP / CH2Cl2 / 2 h / Ambient temperature 4: pyridinium dichromate, pyridine / 5 h / 70 °C View Scheme

Upstream product

• 106315-18-8 Acetic acid (1R,2R,3S)-2-acetoxy-1-[(S)-1-((1R,3aS,3bS,6aS,8S,9R,10aR,10bS,12aS)-8,9-dihydroxy-10a,12a-dimethyl-6-oxo-hexadecahydro-5-oxa-benzo[3,4]cyclohepta[1,2-e]inden-1-yl)-ethyl]-3,4-dimethyl-pentyl ester 
• 10547-89-4 4-(1-methylethyl)furan-2(5H)-one 
• 1418453-68-5 (R)-2-(1,3-dithian-2-yl)-3-methylbutan-1-ol 
• 590-86-3 isovaleraldehyde 
• 1418453-70-9 (S)-2-(3-methylbutan-2-yl)-1,3-dithiane 
• 76976-80-2 Acetic acid (3S,10R,13S,17R)-17-{(S)-1-[(4R,5R)-5-((S)-1,2-dimethyl-propyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-ethyl}-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 
• 81481-15-4 (20S)-6,6-ethylenedioxy-2α,3α-isopropylidenedioxy-5α-pregnane-20-carbaldehyde 
• 91708-76-8 (2R,3S,5α,22R,23R,24S)-6,6-Ethylenedioxy-2,3-isopropylidenedioxyergostane-22,23-diol 
• 111118-49-1 (1R,3aS,3bS,5aS,6aS,9aR,10aR,10bS,12aS)-1-{(S)-1-[(4R,5R)-5-((S)-1,2-Dimethyl-propyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-ethyl}-8,8,10a,12a-tetramethyl-hexadecahydro-7,9-dioxa-dicyclopenta[a,h]phenanthren-5-one 
• 83066-72-2 (2R,3S,5S,8S,9S,10R,13S,14S,17R)-17-{(S)-1-[(4R,5R)-5-((S)-1,2-Dimethyl-propyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-ethyl}-2,3-dihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-6-one 
• 76987-58-1 2α,3α-22R,23R-tetraacetoxy-B-homo-7-oxa-24S-methyl-5α-cholestan-6-one 
• 77027-48-6 2,3,22,23-tetra-O-acetylcastasterone 

Relevant articles and documents

A Novel Synthesis of Brassinolide and Related Compounds

A stereoselective synthesis of the natural promoting steroids, brassinolide, homobrassinolide, and typhasterol is described, which involves construction of a side chain by lactonisation of Z-(5) under acidid conditions to give an α,β-unsaturated δ-lactone (6) with the inversion of the configuration at C-22 of the epoxy steroid in quantitative yield.

STEREOSELECTIVE SYNTHESIS OF THE BRASSINOLIDE SIDE CHAIN: NOVEL SYNTHESIS OF BRASSINOLIDE AND RELATED COMPOUNDS

A stereoselective synthesis of the brassinolide side chain involves the lactonization of Z-10 under acidic condition to give an α,β-unsaturated-δ-lactone 11 with the inversion of the configuration at C-22 of the epoxy steroid in quantitative yield.The 22R,23R,24R-γ-hydroxy-δ-lactone 14 was used as key intermediate for the syntheses of brassinolide (1), homobrassinolide (2), and typhasterol (4) as well as the side chain of the dolicholide (3).

The development and use of a general route to brassinolide, its biosynthetic precursors, metabolites and analogues

A new method for the construction of steroid side chains through the addition of lithium salts of dithianes to a C-22 aldehyde was developed. An efficient one-pot procedure for the preparation of a suitable C-22 aldehyde from commercial epibrassinolide in three steps in 86% isolated yield was described. Enantioselective hydroxymethylation of isovaleraldehyde and Kulinkovich cyclopropanation of silylated Roche esters were used as key steps for the dithiane syntheses. The method was applied for the preparation of brassinolide, its biosynthetic precursors and metabolites. In addition, a number of brassinosteroids with a double bond in the side chain were prepared as precursors for tritiated derivatives for biosynthetic studies.

A general approach to synthesis of labeled brassinosteroids: Preparation of [25,26,27-2h7]brassinolide with 60% isotopic purity from the parent brassinolide

From brassinolide (BL) 1, [25,26,27-2H(n)]BL 10 was synthesized in 5 steps including C-25 hydroxylation, dehydration and catalytic deuteriogenation. In direct oxy-functionalization of tetra-O-acetyl BL 2 with methyl(trifluoromethyl)dioxirane leading to 25-hydroxyl compound 3, 14- hydroxyl, 25-hydroxy-15-oxo and 14,25-dihydroxyl derivatives, 4, 5 and 6, were newly identified; the catalytic deuteriogenation of Δ(25(26))-BL 8 using 5% palladium-on-charcoal resulted in abundant incorporation of deuterium atoms to give 10 with 60% isotopic purity of [25,26,27-2H7]BL.

Improved synthesis of brassinolide

Brassinolide has been synthesized from stigmasterol in an overall yield of 7%. The key step in the synthesis is aldol condensation of 2α,3α-isopropylidenedioxy-6-oxo-23,24-dinor-5α-cholan-22-al with 3-isopropylbut-2-enolide carried out at -78°C, which gives a product with 22R,23R stereochemistry in high yield. Catalytic hydrogenation of this product is highly stereoselective leading to the desired 245 stereochemistry in an intermediate which is readily transformed into brassinolide. Copyright 1996 by the Royal Society of Chemistry.

SYNTHESIS OF BRASSINOLIDE AND ITS ANALOGS

A new version of the synthesis of brassinosteroids of the 28C series is described.It is based on stigmasterol and uses the reaction of steroidal 22-aldehydes with aryl sulfones.

STEREOCONTROLLED SYNTHESIS OF THE BRASSINOLIDE SIDE CHAIN VIA A PYRANONE DERIVATIVE

A new method for assembling the brassinolide side chain from 20-carboxaldehyde 2 was developed via the stereoselective construction of the pyranone moiety as key steps.