Formamide → (2S,5S,6S,14R,15S,16S)-2-(2-hydroxyacetyl)-14-methyl-17-oxapentacyclo[14.2.1.01,5.06,15.09,14]nonadec-9-en-11-one

HRID 1679686Notes

Reaction equation

HRID 1679686 reaction equation
[CH3:1][C@@:2]12[C@H:12]3[C@@H](O)[CH2:14][C@:15]4([CH2:24]O)[C@@H:19]([C:20]([CH2:22][OH:23])=[O:21])[CH2:18][CH2:17][C@H:16]4[C@@H:11]3[CH2:10][CH2:9][C:8]1=[CH:7][C:5](=[O:6])[CH2:4][CH2:3]2.C[C@@]12[C@H]3[C@@H](O)C[C@]4(C=O)[C@@H](C(CO)=O)CC[C@H]4[C@@H]3CCC1=CC(=O)CC2.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OC(=O)C)(=O)C.[CH:71](N)=[O:72]>ClCCCl.CC1CCCCC1.C1(C)C=CC=CC=1.N1C=CC=CC=1>[CH3:1][C@@:2]12[C@H:12]3[C@H:71]4[O:72][CH2:24][C:15]5([C@@H:19]([C:20]([CH2:22][OH:23])=[O:21])[CH2:18][CH2:17][C@H:16]5[C@@H:11]3[CH2:10][CH2:9][C:8]1=[CH:7][C:5](=[O:6])[CH2:4][CH2:3]2)[CH2:14]4

Participants

9

Reactant 5

HCID 713FormamideHCID 5839AldosteroneHCID 6101p-Toluenesulfonic acidHCID 7918Acetic AnhydrideHCID 1122218-Hydroxycorticosterone

Product 1

HCID 188963(2S,5S,6S,14R,15S,16S)-2-(2-hydroxyacetyl)-14-methyl-17-oxapentacyclo[14.2.1.01,5.06,15.09,14]nonadec-9-en-11-one

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 1049PyridineSolventHCID 18008641Methylcyclohexane tolueneSolvent

Procedure

18-deoxyaldosterone was prepared by acid-catalyzed dehydration of 18-hydroxycorticosterone, the latter having been, in turn, prepared biosynthetically employing slices of aldosterone-producing adrenal tissue [Ulick et al, Methods in Enzymology, 36, p. 503 (1975)]. The 11,18-diol (1.0 mg.) in 10 ml 1,2-dichloroethane saturated with p-toluenesulfonic acid was heated under reflux for 30 minutes. The solvent was washed with dilute sodium carbonate and water, dried and evaporated. Chromatographic analysis of the residue revealed 18-deoxyaldosterone as the major product of 18-hydroxycorticosterone along with small amounts of starting material and its etiolactone derivative. 18-deoxyaldosterone migrated at 1.06 (±0.02) the rate of 11-dehydrocorticosterone in the toluene/formamide or methylcyclohexane:toluene (1:1)/formamde paper chromatographic systems. Its properties agreed with those of reference samples prepared by a published method [Kondo et al, JACS 87, 4655 (1965)]. Its 21-acetylated derivative prepared in the usual way with acetic anhydride:pyridine migrated at a slightly faster rate (1.05 ±0.02) than 21-acetoxy-11-dehydrocorticosterone in methylcyclohexane:toluene (1:1)/formamide.

Workup

  1. customproducing adrenal tissue [Ulick et al, Methods in Enzymology, 36, p. 503 (1975)]
  2. temperatureunder reflux for 30 minutes
  3. washThe solvent was washed with dilute sodium carbonate and water
  4. customdried
  5. customevaporated
  6. customprepared by a published method [Kondo et al, JACS 87, 4655 (1965)]

Sources & evidence

ORD record
ord-aefb36672a764b3192f71654925241f6
Source dataset
uspto-grants-1978_03
Patent number
US04081538

Reaction notes

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