Novel HMG-CoA reductase inhibitors

Claim 2

A compound represented by the following general structural formulae (I) and (II): wherein: 0 R is CH 2 0H, CH 2 0 C R 3 , C0 2 R 4 or C NR 6 R 7 ; R 1 and R 3 are independently selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1 . 5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the subsituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3-8 cycloalkylS(O) n , (k) phenylS(O) n , (I) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1-5 acyloxy (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3 . 8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenyIS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C 1-10 alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1-5 alkoxycarbonyl, (k) C 1-5 acyloxy, (I) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; (16) a member selected from (a) piperidinyl, (b) pyrrolidinyl, (c) piperazinyl, (d) morpholinyl, and (e) thiomorpholinyl; and (17) R 5 S in which R 5 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R 2 and R 4 are independently selected from: (1) hydrogen; (2) C 1-5 alkyl; (3) substituted C 1 . 5 alkyl in which the substituent is selected from (a) phenyl, (b) dimethylamino, and (c) acetylamino, and (4) 2,3-dihydroxypropyl; R 6 and R 7 are independently selected from: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-10 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y (i) C 1-10 alkyl S(O) n in which n is 0 to 2, (j) C 3-8 cycloalkyl S(0) n , (k) phenyl S(O) n , (I) substituted phenyl S(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) aminocarbonyl; (7) substituted aminocarbonyl in which one or more substituent(s) is selected from (a) Ci. 5 alkyl, (b) C 3-8 cycloalkyl, (c) phenyl, (d) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; (10) C 1-10 alkylcarbonyl; (11) C 3 . 8 cycloalkylcarbonyl; (12) phenylcarbonyl; (13) substituted phenylcarbonyl in which the substituents are X and Y; and (14) a nitrogen-containing heterocyclic group selected from piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl and thiomorpholinyl; and X and Y independently are hydrogen, halogen, trifluoromethyl, C 1-3 alkyl, nitro, cyano or group selected from: (1) R 8 O(CH 2 ) m in which m is 0 to 3 and R 8 is hydrogen, C 1-3 alkyl or hydroxy-C 2 - 3 alkyl; (2) or in which R 9 is hydrogen, C 1-3 alkyl, hydroxy-C 2 - 3 alkyl, phenyl, naphthyl, amino-C 1-3 alkyl, C 1-3 alkylamino-C 1-3 alkyl, di(C 1-3 alkyl)amino-C 1-3 alkyl, hydroxy-C 2-3 alkylamino-C 1 - 3 alkyl or di(hydroxy-C 2-3 alkyl)amino-C 1-3 alkyl; (3) in which R 10 is hydrogen, C 1 . 3 alkyl, hydroxy-C 2 - 3 alkyl, C 1 . 3 alkoxy-C 1-3 alkyl, phenyl or naphthyl; (4) R 11 R 12 N(CH 2 ) m , or in which R 11 and R 12 independently are hydrogen, C 1-3 alkyl, hydroxy-C 2 - 3 alkyl or together with the nitrogen atom to which they are attached form a heterocyclic group selected from piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl or thiomorpholinyl; (5) R 13 S(0) n (CH 2 ) m in which R 13 is hydrogen, C 1-3 alkyl, amino, C 1-3 alkylamino or di(C 1-3 alkyl)amino; and a, b and c each represent single bonds or one of a, b and c represents a double or both a and c represent double bonds; or a pharmaceutically acceptable salt thereof.

Claim 3

2, A compound of Claim 1 wherein: R 1 and R 3 are independently selected from: (1) C 1-10 alkyl; (2) substituted C1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, and (i) oxo; (3) C 3-8 cycloalkyl; (4) substituent is selected from (a) C 1-10 alkyl, (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy (iv) C 1 . 5 acyloxy, (v) C 1-5 alkoxycarbonyl, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y, and (viii) oxo, (c) halogen, (d) hydroxy, (e) C 1-10 alkoxy, (f) C 1-5 alkoxycarbonyl, (g) C 1-5 acyloxy, (h) phenyl, (i) substituted phenyl in which the substituents are X and Y; (5) phenylamino; (6) substituted phenylamino in which the substituents are X and Y; (7) phenyl C 1-10 alkylamino; (8) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y.

Claim 4

A compound of Claim 2 wherein: R 1 and R 3 are independently selected from:

Claim 5

(1) C 1-10 alkyl;

Claim 6

(1) C 1-10 alkyl;

Claim 7

(2) C 3 . 8 cycloalkyl;

Claim 8

(2) C 3 . 8 cycloalkyl;

Claim 9

(3) phenylamino; and

Claim 10

(3) phenylamino; and

Claim 11

(4) substituted phenylamino in which the substituents are X and Y.

Claim 12

(4) substituted phenylamino in which the substituents are X and Y.

Claim 13

A compound of Claim 3 wherein a and c represent double bonds.

Claim 14

A compound of Claim 4 which is selected from: (1) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (3) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (4) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-carboxy-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (5) 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S)-methyl-6(R)-carboxy-1,2,6,7,8,8a(R)-hexahydronaphthyl-1-(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro2H-pyran-2-one; (6) 6(R)-[2-[8(S)-(2.2-dimethyibutyryloxy)-2(S)-methyl-6(R)-carboxy-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (7) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(N,N-dimethyl)aminocarbonyl-1,2,6,7,8,8a-(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (8) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-aminocarbonyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (9) 6(R)-[2-[8(S)-(2-methylbutyryloxy)2(S)-methyl-6(S)-aminocarbonyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and the corresponding ring opened dihydroxy acids, and esters thereof.

Claim 15

A compound of Claim 3 wherein a, b and c represent single bonds.

Claim 16

A compound of Claim 6 which is selected from: (1) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(2,2-dimethylbutyryloxymethyl)-1,2,3,4,4a-(S),5,6,7,8,8a(S)-decahydronaphthyl-1 (S)]-ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (3) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-carboxy-1,2,3,4,4a(S),5,6,7,8,8a(S)-de- cahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one: (4) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-ethoxycarbonyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (5) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-aminocarbonyl-1,2,3,4,4a(S),5,6, 7,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (6) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(N-cylohexylaminocarbonyl, N-cyclohexyl)-aminocarbonyl-1,2,3,4,4a,(S),5,6,7,8,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and the corresponding ring opened dihydroxy acids, and esters thereof.

Claim 17

A compound of Claim 3 wherein one of a, b or c represents a double bond.

Claim 18

A compound of Claim 8 which is selected from: (1) 6(R)-[2-(8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-hydroxymethyl-1,2,3,4,6,7,8,8a(R)-octahydronaphthyl-1 (S)]ethyll-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-(2,2-dimethylbutyryloxymethyl)-1,2,3,4,6,7,8,8a(R)-octahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one: and the corresponding ring opened dihydroxy acids, and esters thereof.

Claim 19

A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a pharmaceutically acceptable carrier and a nontoxic effective amount of a compound as defined in Claim 1.

Claim 20

A process for the preparation of a compound of Claim I which comprises: (1) contacting a compound of the formulae (A) or (B) wherein a, b, c, R 1 and R 2 are defined in Claim 1 (a) with a growing culture of Nocardia autotrophica for a suitable incubation period (b) with the collected cells of a culture of the bioconverting microorganism; or (c) with a cell-free, enzyme-containing extract from the cells of the bioconverting microorganism (2) followed by isolation, and derivatization if desired.

Claim 21

Claims for the following Contracting States: AT, GR, ES 1. A process for the preparation of a compound represented by the following general structural formulae (I) and (II): wherein: R is CH 2 0H, CH 2 0 R 1 and R 3 are independently selected from: (1) C 1-10 alkyl: (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3 . 8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the subsituents are X and Y, (i) C 1-10 alkylS(O) n in which n is 0 to 2, (j) C 3 - 8 cycloalkylS(O) n , (k) phenylS(O) n , (I) substituted phenylS(O) n in which the substituents are X and Y, and (m) oxo; (3) C 1-10 alkoxy; (4) C 2-10 alkenyl; (5) C 3-8 cycloalkyl; (6) substituted C 3 - 8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy, (iv) C 1-5 alkoxycarbonyl, (v) C 1 . 5 acyloxy (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y (viii) C 1-10 alkylS(O) n , (ix) C 3-8 cycloalkylS(O) n , (x) phenylS(O) n , (xi) substituted phenylS(O) n in which the substituents are X and Y, and (xii) oxo, (c) C i . io alkylS(O) n , (d) C 3-8 cycloalkylS(O) n , (e) phenylS(O) n , (f) substituted phenylS(O) n in which the substituents are X and Y, (g) halogen, (h) hydroxy, (i) C 1-10 alkoxy, (j) C 1 . 5 alkoxycarbonyl, (k) C 1-5 acyloxy, (I) phenyl, and (m) substituted phenyl in which the substituents are X and Y; (7) phenyl; (8) substituted phenyl in which the substituents are X and Y; (9) amino; (10) C 1-5 alkylamino; (11) di(C 1-5 alkyl)amino; (12) phenylamino; (13) substituted phenylamino in which the substituents are X and Y; (14) phenyl C 1-10 alkylamino; (15) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y; (16) a member selected from (a) piperidinyl, (b) pyrrolidinyl, (c) piperazinyl, (d) morpholinyl, and (e) thiomorpholinyl; and (17) R 5 S in which R 5 is selected from (a) C 1-10 alkyl, (b) phenyl, and (c) substituted phenyl in which the substituents are X and Y; R 2 and R 4 are independently selected from: (1) hydrogen; (2) C 1-5 alkyl; (3) substituted C 1 . 5 alkyl in which the substituent is selected from (a) phenyl, (b) dimethylamino, and (c) acetylamino, and (4) 2,3-dihydroxypropyl; R 6 and R 7 are independently selected from: (1) hydrogen; (2) C 1-10 alkyl; (3) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-10 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3-8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y (i) C 1-10 alkyl S(O) n in which n is 0 to 2, (j) C 3 . 8 cycloalkyl S(O) n , (k) phenyl S(O) n , (I) substituted phenyl S(O) n in which the substituents are X and Y, and (m) oxo; (4) C 2 - 10 alkenyl; (5) C 3-8 cycloalkyl; (6) aminocarbonyl; (7) substituted aminocarbonyl in which one or more substituent(s) is selected from (a) C 1-5 alkyl, (b) C 3-8 cycloalkyl, (c) phenyl, (d) substituted phenyl in which the substituents are X and Y; (8) phenyl; (9) substituted phenyl in which the substituents are X and Y; (10) C 1-10 alkylcarbonyl; (11) C 3-8 cycloalkylcarbonyl; (12) phenylcarbonyl; (13) substituted phenylcarbonyl in which the substituents are X and Y; and (14) a nitrogen-containing heterocyclic group selected from piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl and thiomorpholinyl; and X and Y independently are hydrogen, halogen, trifluoromethyl, C 1 . 3 alkyl, nitro, cyano or group selected from: (1) R 8 O(CH 2 ) m in which m is 0 to 3 and R 8 is hydrogen, C 1-3 alkyl or hydroxy-C 2-3 alkyl; (2) or in which R 9 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, phenyl, naphthyl, amino-C 1-3 alkyl, C 1-3 alkylamino-C 1-3 alkyl, di(C 1-3 alkyl)amino-C 1-3 alkyl, hydroxy-C 2 . 3 alkylamino-C 1- 3 alkyl or di(hydroxy-C 2-3 alkyl) amino-C 1-3 alkyl; (3) in which R 10 is hydrogen, C 1-3 alkyl, hydroxy-C 2-3 alkyl, C 1-3 alkoxy-C 1-3 alkyl, phenyl or naphthyl; (4) R 11 R 12 N(CH 2 ) m , R 11 R 12 N or in which R 11 and R 12 independently are hydrogen, C 1-3 alkyl, hydroxy-C 2 . 3 alkyl or together with the nitrogen atom to which they are attached form a heterocyclic group selected from piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl or thiomorpholinyl; (5) R 13 S(0) n (CH 2 ) m in which is hydrogen, C 1 - 3 alkyl, amino, C 1-3 alkyl-amino or di(C 1-3 alkyl)amino; and a, b and c each represent single bonds or one of a,b and c represents a double bond or both a and c represent double bonds; or a pharmaceutically acceptable salt thereof which comprises: (1) contacting a compound of the formulae (A) or (B) wherein a, b, c, R 1 and R 2 are defined above (a) with a growing culture of Nocardia autotrophica for a suitable incubation period (b) with the collected cells of a culture of the bioconverting microorganism; or (c) with a cell-free, enzyme-containing extract from the cells of the bioconverting microorganism (2) followed by isolation, and derivatization if desired.

Claim 22

A process of Claim 1 wherein: R 1 and R 3 are independently selected from: (1) C 1-10 alkyl; (2) substituted C 1-10 alkyl in which one or more substituent(s) is selected from (a) halogen, (b) hydroxy, (c) C 1-10 alkoxy, (d) C 1-5 alkoxycarbonyl, (e) C 1-5 acyloxy, (f) C 3 - 8 cycloalkyl, (g) phenyl, (h) substituted phenyl in which the substituents are X and Y, and (i) oxo; (3) C 3-8 cycloalkyl; (4) substituted C 3-8 cycloalkyl in which one substituent is selected from (a) C 1-10 alkyl, (b) substituted C 1-10 alkyl in which the substituent is selected from (i) halogen, (ii) hydroxy, (iii) C 1-10 alkoxy (iv) C 1-5 acyloxy, (v) C 1-5 alkoxycarbonyl, (vi) phenyl, (vii) substituted phenyl in which the substituents are X and Y, and (viii) oxo, (c) halogen, (d) hydroxy, (e) C 1-10 alkoxy, (f) C 1-5 alkoxycarbonyl, (g) C 1 - 5 acyloxy, (h) phenyl, (i) substituted phenyl in which the substituents are X and Y; (5) phenylamino; (6) substituted phenylamino in which the substituents are X and Y; (7) phenyl C 1-10 alkylamino; (8) substituted phenyl C 1-10 alkylamino in which the substituents are X and Y.

Claim 23

A process of Claim 2 wherein: R 1 and R 3 are independently selected from: (1) C 1-10 alkyl; (2) C 3 - 8 cycloalkyl; (3) Phenylamino; and (4) substituted phenylamino in which the substituents are X and Y.

Claim 24

A process of Claim 3 wherein a and c represent double bonds.

Claim 25

A process of Claim 4 in which the compound is selected from: (1) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-Pyran-2-one; (3) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-hydroxymethyl-1,2,6,7,8,8a(R)-hexahydronaPhthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (4) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-carboxy-1,2,6,7,8,Ba(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (5) 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S)-methyl-6(R)-carboxy-1,2,6,7,8,8a(R)-hexahydronaphthyl-1-(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (6) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-carboxy-1,2,6,7,8,8a(R)-hexahydronaPhthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (7) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(N,N-dimethyl)aminocarbonyl-1,2,6,7,8,8a-(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (8) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-aminocarbonyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (9) 6(R)-[2-[8(S)-(2-methylbutyryloxy)-2(S)-methyl-6(S)-aminocarbonyl-1,2,6,7,8,8a(R)-hexahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;and the corresponding ring opened dihydroxy acids, and esters thereof.

Claim 26

A process of Claim 3 wherein a , b and c represent single bonds.

Claim 27

A process of Claim 6 in which the compound is selected from: (1) 6(R)-[2-[8(S)-(2;2-dimethylbutyryloxy)-2(S)-methyl-6(S)-hydroxymethyl-1,2,3,4,4a(S),5,6,7,8,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(2,2-dimethylbutyryloxymethyl) -1,2,3,4,4a-(S),5,6,7,8,8a(S)-decahydronaphthyt-1-(S)]-ethy)]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (3) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-carboxy-1,2,3,4,4a(S),5,6,7,8,8a (S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (4) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-ethoxycarbonyl-1,2,3,4,4a(S),5,6, 7,8,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (5) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-aminocarbonyl-1,2,3,4,4a(S),5,6, 7,8a(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-Pyran-2-one; (6) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(S)-(N-cylohexylaminocarbonyl, N-cyclohexyl)-aminocarbonyl-1,2,3,4,4a,(S),5,6,7,8,8a-(S)-decahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; and the corresponding ring opened dihydroxy acids, and esters thereof.

Claim 28

A process of Claim 3 wherein one of a , b or c represents a double bond.

Claim 29

A process of Claim 8 in which the compound is selected from: (1) 6(R)-[2-(8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-hydroxymethyl-1,2;3,4,6,7,8,8a(R)-octahydronaphthyl-1 (S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one; (2) 6(R)-[2-[8(S)-(2,2-dimethylbutyryloxy)-2(S)-methyl-6(R)-(2,2-dimethylbutyryloxymethyl)-1,2,3,4,6,7,8,8a(R)-octahydronaphthyl-1(S)]ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one;and the corresponding ring opened dihydroxy acids, and esters thereof.