Studies on the Synthesis of Phlegmarine-type Lycopodium

Alkaloids. Enantioselective Synthesis of (–)-Cermizine B,

(+)-Serratezomine E, and (+)-Luciduline

Alexandre Pinto,† Miriam Piccichè, † Rosa Griera,† Elies Molins,‡ Joan Bosch,†
and Mercedes Amat*,†

†
Laboratory of Organic Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of
Biomedicine (IBUB), University of Barcelona, 080028-Barcelona, Spain
‡
Institut de Ciència de Materials de Barcelona (ICMAB, CSIC), Campus UAB, 08193-Bellaterra,
Spain

I) Copies of 1H and 13C NMR spectra: pages S2-S25

II) X- ray crystallographic data for compound 3: pages S26-S36

S1 
I) Copies of 1H and 13C NMR spectra

S2 
  
 

S3 
S4 
S5 
 C6H5
O
O N O

H
6
100.6 MHz; CDCl3

S6 
S7 
  
 
 

 
 

S8 
 C6H5
O
O N

H
OH
400 MHz; CDCl3

C6H5
O
O N

H
OH
100.6 MHz; CDCl3

S9 
 C6H5
O
O N

H
8 OTIPS
400 MHz; CDCl3

 
 

S10 
  
 
 
 
 
 
 

S11 
 

 
 

S12 
  
 

S13 
  
 

S14 
  
 

S15 
  
 

S16 
  
 

C6H5
O
O N

H H
N O

100.6 MHz; CDCl3

S17 
  
 

S18 
  
 

S19 
  
 

S20 
  
 

S21 
  
 

S22 
 Me
H
O N

H
O
33 OMe
400 MHz; CDCl3

 
 

Me
H
O N

H
O
33 OMe
100.6 MHz; CDCl3

S23 
  
 

S24 
  
 

 
 
 
 
 
 

S25 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
II) X- ray crystallographic data for compound 3
 
 
   

S26 
Crystal structure and data of (3R,7aS,10R,11aS)‐10‐Hydroxy‐5‐oxo‐3‐phenyl‐2,3,5,6,7,7a,10,11‐
octahydrooxazolo[2,3‐j] quinoline (3) (CCDC 1837026), Displacement ellipsoids are drawn at the 
50% probability level. 
 
 
 
Figure S1.  

S27 
Table S1. Crystal data and structure refinement for 3 Jb127.
Identification code Jb127
Empirical formula C17 H19 N O3
Formula weight 285.33
Temperature 293(2) K
Wavelength 0.71073 Å
Crystal system Monoclinic
Space group C2
Unit cell dimensions a = 22.070(5) Å = 90°.
b = 6.411(3) Å = 113.74(2)°.
c = 11.639(3) Å  = 90°.
Volume 1507.5(9) Å3
Z 4
Density (calculated) 1.257 Mg/m3
Absorption coefficient 0.086 mm-1
F(000) 608
Crystal size 0.45 x 0.39 x 0.21 mm3
Theta range for data collection 1.911 to 24.971°.
Index ranges -24<=h<=26, 0<=k<=7, -13<=l<=0
Reflections collected 2617
Independent reflections 1456 [R(int) = 0.0325]
Completeness to theta = 24.971° 99.5 %
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 1456 / 6 / 196
Goodness-of-fit on F2 1.065
Final R indices [I>2sigma(I)] R1 = 0.0445, wR2 = 0.1056
R indices (all data) R1 = 0.0751, wR2 = 0.1175
Largest diff. peak and hole 0.134 and -0.210 e.Å-3

S28 
Table S2. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103)
for Jb127. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
________________________________________________________________________________
x y z U(eq)
________________________________________________________________________________
O(2) 2530(1) 5535(5) 3355(2) 70(1)
O(8) 114(2) -1504(7) 1316(3) 102(1)
O(13) 1474(1) -195(4) 2773(2) 61(1)
N(1) 1698(1) 3208(5) 2646(2) 43(1)
C(2) 2046(2) 4738(6) 3454(3) 51(1)
C(3) 1824(2) 5392(7) 4453(3) 66(1)
C(4) 1178(2) 4419(7) 4353(4) 69(1)
C(5) 1173(2) 2089(7) 4068(3) 56(1)
C(6) 583(2) 966(9) 4100(4) 78(2)
C(7) 93(2) 231(11) 3107(4) 95(2)
C(8) 38(2) 483(10) 1805(4) 79(2)
C(9) 533(2) 2087(8) 1738(3) 59(1)
C(10) 1208(2) 1831(6) 2809(3) 46(1)
C(11) 1975(2) 2165(6) 1844(3) 45(1)
C(12) 1750(2) -110(7) 1857(4) 65(1)
C(14) 1758(1) 3013(6) 526(3) 42(1)
C(15) 1937(2) 1954(7) -326(3) 55(1)
C(16) 1730(2) 2625(8) -1551(4) 70(1)
C(17) 1357(2) 4413(9) -1920(4) 77(1)
C(18) 1189(2) 5489(8) -1081(4) 73(1)
C(19) 1386(2) 4793(6) 137(3) 52(1)
________________________________________________________________________________

S29 
Table S3. Bond lengths [Å] and angles [°] for Jb127.
_____________________________________________________
O(2)-C(2) 1.233(4)
O(8)-C(8) 1.432(7)
O(8)-H(8A) 0.82(2)
O(8)-H(8B) 0.835(18)
O(13)-C(12) 1.427(4)
O(13)-C(10) 1.432(5)
N(1)-C(2) 1.361(5)
N(1)-C(11) 1.466(4)
N(1)-C(10) 1.467(4)
C(2)-C(3) 1.492(5)
C(3)-C(4) 1.517(6)
C(3)-H(3A) 0.9700
C(3)-H(3B) 0.9700
C(4)-C(5) 1.529(6)
C(4)-H(4A) 0.9700
C(4)-H(4B) 0.9700
C(5)-C(6) 1.501(5)
C(5)-C(10) 1.508(5)
C(5)-H(5) 0.9800
C(6)-C(7) 1.312(6)
C(6)-H(6) 0.9300
C(7)-C(8) 1.480(6)
C(7)-H(7) 0.9300
C(8)-C(9) 1.524(6)
C(8)-H(8) 0.9800
C(9)-C(10) 1.519(5)
C(9)-H(9A) 0.9700
C(9)-H(9B) 0.9700
C(11)-C(14) 1.512(5)
C(11)-C(12) 1.543(6)
C(11)-H(11) 0.9800
C(12)-H(12A) 0.9700
C(12)-H(12B) 0.9700
C(14)-C(19) 1.372(5)
C(14)-C(15) 1.384(5)
C(15)-C(16) 1.379(6)

S30 
C(15)-H(15) 0.9300
C(16)-C(17) 1.376(7)
C(16)-H(16) 0.9300
C(17)-C(18) 1.363(6)
C(17)-H(17) 0.9300
C(18)-C(19) 1.380(5)
C(18)-H(18) 0.9300
C(19)-H(19) 0.9300

C(8)-O(8)-H(8A) 111(3)
C(8)-O(8)-H(8B) 107.4(19)
H(8A)-O(8)-H(8B) 104(10)
C(12)-O(13)-C(10) 106.8(3)
C(2)-N(1)-C(11) 120.3(3)
C(2)-N(1)-C(10) 125.7(3)
C(11)-N(1)-C(10) 109.0(3)
O(2)-C(2)-N(1) 120.2(3)
O(2)-C(2)-C(3) 121.7(3)
N(1)-C(2)-C(3) 118.1(3)
C(2)-C(3)-C(4) 114.6(3)
C(2)-C(3)-H(3A) 108.6
C(4)-C(3)-H(3A) 108.6
C(2)-C(3)-H(3B) 108.6
C(4)-C(3)-H(3B) 108.6
H(3A)-C(3)-H(3B) 107.6
C(3)-C(4)-C(5) 110.1(3)
C(3)-C(4)-H(4A) 109.6
C(5)-C(4)-H(4A) 109.6
C(3)-C(4)-H(4B) 109.6
C(5)-C(4)-H(4B) 109.6
H(4A)-C(4)-H(4B) 108.2
C(6)-C(5)-C(10) 110.8(3)
C(6)-C(5)-C(4) 113.2(4)
C(10)-C(5)-C(4) 108.6(3)
C(6)-C(5)-H(5) 108.0
C(10)-C(5)-H(5) 108.0
C(4)-C(5)-H(5) 108.0
C(7)-C(6)-C(5) 124.5(4)

S31 
C(7)-C(6)-H(6) 117.7
C(5)-C(6)-H(6) 117.7
C(6)-C(7)-C(8) 124.1(4)
C(6)-C(7)-H(7) 117.9
C(8)-C(7)-H(7) 117.9
O(8)-C(8)-C(7) 109.6(5)
O(8)-C(8)-C(9) 112.3(3)
C(7)-C(8)-C(9) 111.2(4)
O(8)-C(8)-H(8) 107.9
C(7)-C(8)-H(8) 107.9
C(9)-C(8)-H(8) 107.9
C(10)-C(9)-C(8) 111.9(3)
C(10)-C(9)-H(9A) 109.2
C(8)-C(9)-H(9A) 109.2
C(10)-C(9)-H(9B) 109.2
C(8)-C(9)-H(9B) 109.2
H(9A)-C(9)-H(9B) 107.9
O(13)-C(10)-N(1) 102.2(2)
O(13)-C(10)-C(5) 108.0(3)
N(1)-C(10)-C(5) 112.9(3)
O(13)-C(10)-C(9) 110.6(3)
N(1)-C(10)-C(9) 111.1(3)
C(5)-C(10)-C(9) 111.6(3)
N(1)-C(11)-C(14) 116.0(3)
N(1)-C(11)-C(12) 101.9(3)
C(14)-C(11)-C(12) 112.2(3)
N(1)-C(11)-H(11) 108.8
C(14)-C(11)-H(11) 108.8
C(12)-C(11)-H(11) 108.8
O(13)-C(12)-C(11) 106.2(3)
O(13)-C(12)-H(12A) 110.5
C(11)-C(12)-H(12A) 110.5
O(13)-C(12)-H(12B) 110.5
C(11)-C(12)-H(12B) 110.5
H(12A)-C(12)-H(12B) 108.7
C(19)-C(14)-C(15) 118.5(3)
C(19)-C(14)-C(11) 122.5(3)
C(15)-C(14)-C(11) 119.0(3)

S32 
C(16)-C(15)-C(14) 121.1(4)
C(16)-C(15)-H(15) 119.4
C(14)-C(15)-H(15) 119.4
C(17)-C(16)-C(15) 119.3(4)
C(17)-C(16)-H(16) 120.3
C(15)-C(16)-H(16) 120.3
C(18)-C(17)-C(16) 120.0(4)
C(18)-C(17)-H(17) 120.0
C(16)-C(17)-H(17) 120.0
C(17)-C(18)-C(19) 120.6(4)
C(17)-C(18)-H(18) 119.7
C(19)-C(18)-H(18) 119.7
C(14)-C(19)-C(18) 120.5(3)
C(14)-C(19)-H(19) 119.8
C(18)-C(19)-H(19) 119.8
_____________________________________________________________

S33 
Table S4. Anisotropic displacement parameters (Å2x 103)for Jb127. The anisotropic
displacement factor exponent takes the form: -22[ h2a*2U11 + ... + 2 h k a* b* U12 ]
______________________________________________________________________________
U11 U22 U33 U23 U13 U12
______________________________________________________________________________
O(2) 68(2) 76(2) 57(2) -5(1) 17(1) -28(2)
O(8) 104(3) 122(3) 82(2) -19(2) 41(2) -62(3)
O(13) 74(2) 49(2) 72(2) 10(1) 40(1) -1(2)
N(1) 39(1) 47(2) 43(1) 3(2) 16(1) -4(2)
C(2) 55(2) 50(2) 35(2) 5(2) 7(2) -6(2)
C(3) 85(3) 64(3) 44(2) -6(2) 21(2) -9(2)
C(4) 79(3) 87(4) 46(2) 0(2) 32(2) 15(3)
C(5) 51(2) 74(3) 41(2) 10(2) 18(2) -3(2)
C(6) 71(3) 121(4) 52(2) 8(3) 35(2) -14(3)
C(7) 63(2) 157(6) 70(3) 8(4) 33(2) -30(4)
C(8) 53(2) 124(4) 60(3) -1(3) 22(2) -25(3)
C(9) 49(2) 87(3) 40(2) 6(2) 17(2) -7(2)
C(10) 43(2) 49(2) 43(2) 4(2) 15(1) -2(2)
C(11) 40(2) 48(2) 50(2) 1(2) 21(2) 0(2)
C(12) 86(3) 48(2) 75(2) 8(2) 47(2) 5(2)
C(14) 38(2) 43(2) 51(2) -3(2) 22(1) -5(2)
C(15) 52(2) 55(2) 68(2) -8(2) 34(2) -2(2)
C(16) 69(2) 91(4) 62(3) -20(2) 40(2) -9(3)
C(17) 80(3) 105(4) 52(2) 14(3) 32(2) 19(3)
C(18) 85(3) 81(3) 63(2) 21(2) 39(2) 28(3)
C(19) 61(2) 50(2) 54(2) 2(2) 32(2) 8(2)
______________________________________________________________________________

S34 
Table S5. Hydrogen coordinates ( x 104) and isotropic displacement parameters (Å2x 103)
for Jb127.
________________________________________________________________________________
x y z U(eq)
________________________________________________________________________________

H(8A) 50(70) -1420(70) 570(40) 153

H(8B) 513(9) -1830(70) 1670(90) 153
H(3A) 1776 6897 4425 79
H(3B) 2167 5032 5264 79
H(4A) 810 5100 3690 82
H(4B) 1127 4615 5135 82
H(5) 1572 1465 4706 67
H(6) 564 778 4877 94
H(7) -242 -495 3229 113
H(8) -408 997 1293 95
H(9A) 576 1940 946 71
H(9B) 367 3478 1769 71
H(11) 2459 2222 2257 54
H(12A) 1422 -499 1037 78
H(12B) 2123 -1054 2079 78
H(15) 2200 769 -68 66
H(16) 1842 1876 -2121 84
H(17) 1219 4888 -2741 92
H(18) 939 6703 -1332 88
H(19) 1265 5535 699 63
________________________________________________________________________________

S35 
Table S6. Hydrogen bonds for Jb127 [Å and °].
____________________________________________________________________________
D-H...A d(D-H) d(H...A) d(D...A) <(DHA)
____________________________________________________________________________
O(8)-H(8A)...O(8)#1 0.82(2) 2.08(2) 2.898(7) 175(4)
O(8)-H(8B)...O(13) 0.835(18) 2.25(2) 2.913(4) 137(3)
C(3)-H(3A)...O(13)#2 0.97 2.57 3.348(5) 137.8
C(5)-H(5)...O(2)#3 0.98 2.40 3.356(5) 164.2
C(12)-H(12B)...O(2)#4 0.97 2.59 3.374(5) 137.8
____________________________________________________________________________
Symmetry transformations used to generate equivalent atoms:
#1 -x,y,-z #2 x,y+1,z #3 -x+1/2,y-1/2,-z+1
#4 x,y-1,z

S36