Intramolecular [2 + 2] Photocycloaddition of Altrenogest: Confirmation of Product Structure, Theoretical Mechanistic Insight, and Bioactivity Assessment.
Pflug, Nicholas C.; Patterson, Eric V.; Martinović-Weigelt, Dalma; Kolodziej, Edward P.; Gloer, James B.; McNeill, Kristopher; Cwiertny, David M.; Wammer, Kristine H.; The Journal of organic chemistry 84 (2019) 11366–11371; doi:10.1021/acs.joc.9b02070

data_4033856
_publ_section_title
;
 Intramolecular [2 + 2] Photocycloaddition of Altrenogest: Confirmation of
 Product Structure, Theoretical Mechanistic Insight, and Bioactivity
 Assessment.
;
_journal_issue                   17
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              11366
_journal_page_last               11371
_journal_paper_doi               10.1021/acs.joc.9b02070
_journal_volume                  84
_journal_year                    2019
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C21 H26 O2, 0.5(H2 O)'
_chemical_formula_sum            'C21 H27 O2.5'
_chemical_formula_weight         319.42
_chemical_name_systematic
'2a-hydroxy-10e-methyl-1a,2,2a,3,4,4a,4b,5,6,9,10,10c,10d,10e-tetradecahydrocyclobuta[3,4]cyclopenta[1,7]indeno[5,6-a]naphthalen-8(1H)-one hydrate'
_space_group_crystal_system      hexagonal
_space_group_IT_number           170
_space_group_name_Hall           'P 65'
_space_group_name_H-M_alt        'P 65'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-07-29
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            6
_cell_length_a                   15.63070(10)
_cell_length_b                   15.63070(10)
_cell_length_c                   12.53510(10)
_cell_measurement_reflns_used    53607
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      79.2040
_cell_measurement_theta_min      3.2460
_cell_volume                     2652.26(3)
_computing_cell_refinement       'CrysAlisPro 1.171.39.31d (Rigaku OD, 2017)'
_computing_data_collection       'CrysAlisPro 1.171.39.31d (Rigaku OD, 2017)'
_computing_data_reduction        'CrysAlisPro 1.171.39.31d (Rigaku OD, 2017)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector_type            'Pilatus 300K'
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -45.00  41.00   0.50    0.30    --  -34.00  44.00 -24.16  172
  2  \w    -44.00 -19.00   0.50    0.30    --  -42.00 -76.00  86.35   50
  3  \w    -59.00 -29.00   0.50    0.30    --  -54.00 -81.00  97.01   60
  4  \w    -71.00 -45.00   0.50    1.10    --  -70.00 -79.00  20.15   52
  5  \w    -69.00 -39.00   0.50    1.10    --  -66.00 -83.00  -4.62   60
  6  \w    -63.00 -36.00   0.50    0.30    --  -49.37 -45.00 -79.29   54
  7  \w    -78.00 -47.00   0.50    1.10    --  -70.00 -74.00 -61.85   62
  8  \w    -74.00 -48.00   0.50    1.10    --  -70.00 -73.00-116.89   52
  9  \w    -72.00 -46.00   0.50    1.10    --  -70.00 -77.00-120.00   52
 10  \w    -77.00 -46.00   0.50    1.10    --  -70.00 -78.00 -72.74   62
 11  \w    -71.00 -46.00   0.50    1.10    --  -70.00 -78.00 -39.68   50
 12  \w    -98.00 -36.00   0.50    0.30    --  -49.37 -38.00  30.00  124
 13  \w    -83.00 -45.00   0.50    1.10    --  -70.00 -80.00  61.76   76
 14  \w    -72.00 -44.00   0.50    1.10    --  -70.00 -81.00 151.76   56
 15  \w   -115.00 -89.00   0.50    1.10    --  -70.00 -78.00 -39.68   52
 16  \w   -122.00 -67.00   0.50    0.30    --  -49.37 -45.00 -79.29  110
 17  \w    -78.00 -46.00   0.50    1.10    --  -70.00 -77.00-150.00   64
 18  \w    -83.00 -45.00   0.50    1.10    --  -70.00 -79.00-175.82   76
 19  \w   -109.00 -36.00   0.50    0.30    --  -49.37 -38.00-180.00  146
 20  \w    -46.00   1.00   0.50    1.10    --  -70.00  57.00 -90.00   94
 21  \w    -84.00 -31.00   0.50    0.30    --  -26.00 148.00  77.97  106
 22  \w    -47.00  30.00   0.50    0.30    --  -26.00  75.00 179.39  154
 23  \w     34.00  66.00   0.50    0.30    --   49.37  57.00  30.00   64
 24  \w     46.00  71.00   0.50    0.30    --   70.00  78.00  19.60   50
 25  \w     60.00  90.00   0.50    0.30    --   78.00  65.00  32.92   60
 26  \w     80.00 119.00   0.50    1.10    --   98.00  62.00  46.91   78
 27  \w    125.00 167.00   0.50    1.10    --   98.00  62.00  46.91   84
 28  \w    142.00 168.00   0.50    1.10    --  110.00  77.00  90.00   52
 29  \w    152.00 177.00   0.50    1.10    --  110.00  38.00  90.00   50
 30  \w    135.00 171.00   0.50    1.10    --  110.00  77.00  60.00   72
 31  \w    123.00 149.00   0.50    1.10    --   82.00  72.00 115.35   52
 32  \w     96.00 121.00   0.50    0.30    --   54.00  82.00 157.94   50
 33  \w     89.00 177.00   0.50    1.10    --  110.00  72.00 173.84  176
 34  \w     99.00 138.00   0.50    1.10    --  110.00  38.00  90.00   78
 35  \w     96.00 178.00   0.50    1.10    --  110.00  57.00  30.00  164
 36  \w    151.00 177.00   0.50    1.10    --  110.00  77.00 -30.00   52
 37  \w     94.00 142.00   0.50    1.10    --  110.00  57.00-120.00   96
 38  \w    136.00 175.00   0.50    1.10    --  110.00  38.00-180.00   78
 39  \w    108.00 134.00   0.50    1.10    --  110.00  38.00-180.00   52
 40  \w     90.00 177.00   0.50    1.10    --  110.00  77.00-120.00  174
 41  \w     95.00 167.00   0.50    1.10    --  110.00  57.00 -30.00  144
 42  \w     87.00 172.00   0.50    1.10    --  110.00  77.00 -60.00  170
 43  \w     93.00 178.00   0.50    1.10    --  110.00  65.00 -87.12  170
 44  \w     86.00 175.00   0.50    1.10    --  110.00  77.00-150.00  178
 45  \w     87.00 172.00   0.50    1.10    --  110.00  77.00   0.00  170
 46  \w     87.00 136.00   0.50    1.10    --  110.00  77.00  90.00   98
 47  \w     88.00 142.00   0.50    1.10    --  110.00  77.00 150.00  108
 48  \w     86.00 112.00   0.50    1.10    --  110.00  77.00  60.00   52
 49  \w     86.00 177.00   0.50    1.10    --  110.00  77.00 120.00  182
 50  \w     86.00 139.00   0.50    1.10    --  110.00  77.00 -30.00  106
 51  \w     73.00 102.00   0.50    1.10    --   94.00  74.00 -58.77   58
 52  \w     76.00 101.00   0.50    1.10    --   98.00  73.00 -65.11   50
 53  \w     50.00  76.00   0.50    0.30    --   74.00  78.00  38.09   52
 54  \w     49.00  90.00   0.50    0.30    --   74.00  80.00  78.56   82
 55  \w     61.00  92.00   0.50    1.10    --   82.00  72.00 115.35   62
 56  \w     48.00  86.00   0.50    0.30    --   74.00  83.00 115.64   76
 57  \w     56.00  87.00   0.50    1.10    --   82.00  83.00 148.69   62
 58  \w     50.00  86.00   0.50    0.30    --   74.00  79.00  93.12   72
 59  \w     34.00  62.00   0.50    0.30    --   49.37  57.00 150.00   56
 60  \w     29.00  55.00   0.50    0.30    --   54.00  82.00 157.94   52
 61  \w     20.00  45.00   0.50    0.30    --   50.00  90.00  55.81   50
 62  \w     26.00  55.00   0.50    0.30    --   49.37  77.00  30.00   58
 63  \w     35.00  67.00   0.50    0.30    --   49.37  57.00 -60.00   64
 64  \w     52.00  79.00   0.50    0.30    --   78.00  83.00 -81.47   54
 65  \w     57.00 110.00   0.50    1.10    --   82.00  81.00-155.85  106
 66  \w     34.00  64.00   0.50    0.30    --   49.37  57.00-120.00   60
 67  \w     20.00  45.00   0.50    0.30    --   50.00  90.00-100.79   50
 68  \w     29.00  55.00   0.50    0.30    --   54.00  81.00-131.49   52
 69  \w     45.00  73.00   0.50    1.10    --  110.00 -57.00 -60.00   56
 70  \w     53.00  98.00   0.50    1.10    --  110.00 -99.00-120.00   90
 71  \w     46.00  91.00   0.50    1.10    --  110.00 -99.00 -30.00   90
 72  \w     46.00 110.00   0.50    1.10    --  110.00 -99.00  60.00  128
 73  \w     48.00 110.00   0.50    1.10    --  110.00 -99.00 150.00  124
 74  \w     47.00 133.00   0.50    1.10    --  110.00 -77.00 150.00  172
 75  \w     39.00 117.00   0.50    1.10    --  110.00-125.00  60.00  156
 76  \w     40.00 104.00   0.50    1.10    --  110.00 -99.00 -60.00  128
 77  \w     46.00  91.00   0.50    1.10    --  110.00 -99.00  90.00   90
 78  \w    -93.00 -15.00   0.50    1.10    --  -70.00 125.00  30.00  156
 79  \w   -135.00-110.00   0.50    1.10    --  -70.00 -79.00-175.82   50
 80  \w   -131.00-106.00   0.50    1.10    --  -70.00 -73.00-116.89   50
 81  \w   -132.00-107.00   0.50    1.10    --  -70.00 -74.00 -61.85   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, Pilatus 300K'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0425
_diffrn_reflns_av_unetI/netI     0.0121
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       19
_diffrn_reflns_limit_h_min       -19
_diffrn_reflns_limit_k_max       19
_diffrn_reflns_limit_k_min       -19
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            70373
_diffrn_reflns_point_group_measured_fraction_full 0.986
_diffrn_reflns_point_group_measured_fraction_max 0.966
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.533
_diffrn_reflns_theta_min         4.808
_exptl_absorpt_coefficient_mu    0.603
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.719
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.31d (Rigaku Oxford Diffraction, 2017)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light brown'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    brown
_exptl_crystal_density_diffrn    1.200
_exptl_crystal_description       plank
_exptl_crystal_F_000             1038
_exptl_crystal_size_max          0.425
_exptl_crystal_size_mid          0.11
_exptl_crystal_size_min          0.069
_refine_diff_density_max         0.306
_refine_diff_density_min         -0.180
_refine_diff_density_rms         0.049
_refine_ls_abs_structure_details
;
 Flack x determined using 1658 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.08(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     252
_refine_ls_number_reflns         3711
_refine_ls_number_restraints     55
_refine_ls_restrained_S_all      1.049
_refine_ls_R_factor_all          0.0352
_refine_ls_R_factor_gt           0.0349
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0620P)^2^+0.4401P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0945
_refine_ls_wR_factor_ref         0.0948
_reflns_Friedel_coverage         0.851
_reflns_Friedel_fraction_full    0.972
_reflns_Friedel_fraction_max     0.931
_reflns_number_gt                3663
_reflns_number_total             3711
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo9b02070_si_002.cif
_cod_data_source_block           u210818_1_1
_cod_original_cell_volume        2652.25(4)
_cod_original_formula_sum        'C21 H27 O2.50'
_cod_database_code               4033856
_shelx_shelxl_version_number     2018/3
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All C(H,H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups, All O(H,H) groups
2. Restrained distances
 O1-H1
 0.93 with sigma of 0.02
 H3AA-H3AB
 1.344 with sigma of 0.001
 O3A-H3AA = O3A-H3AB
 0.85 with sigma of 0.001
 O3-H3B = O3-H3A
 0.85 with sigma of 0.001
 H3A-H3B
 1.344 with sigma of 0.001
 C2-C1 \\sim C2A-C1
 with sigma of 0.02
 C3-C2 \\sim C3-C2A
 with sigma of 0.02
3. Rigid body (RIGU) restrains
 C10, C1, C2A, C2, C3, O2, C4
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
4. Others
 Sof(H1BC)=Sof(H1BD)=Sof(C2A)=Sof(H2AA)=Sof(H2AB)=1-FVAR(1)
 Sof(H1AA)=Sof(H1AB)=Sof(C2)=Sof(H2A)=Sof(H2B)=FVAR(1)
 Fixed Sof: O3(0.25) H3A(0.25) H3B(0.25) O3A(0.25) H3AA(0.25) H3AB(0.25)
5.a Ternary CH refined with riding coordinates:
 C21(H21), C11(H11), C12(H12), C14(H14), C8(H8)
5.b Secondary CH2 refined with riding coordinates:
 C20(H20A,H20B), C22(H22A,H22B), C16(H16A,H16B), C15(H15A,H15B), C6(H6A,H6B),
 C7(H7A,H7B), C1(H1AA,H1AB), C1(H1BC,H1BD), C2(H2A,H2B), C2A(H2AA,H2AB)
5.c Aromatic/amide H refined with riding coordinates:
 C4(H4)
5.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C)
;
_shelx_res_checksum              672
_shelx_hkl_checksum              41684
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
- Detector area scaling
;